Vitamin D status in growing dairy goats and sheep: Influence of ultraviolet B radiation on bone metabolism and calcium homeostasis.

The aim of this study was to investigate how controlled UVB irradiation in combination with reduced nutritional vitamin D (vitD) supply affects vitD status and Ca metabolism of growing goats and sheep. The hypothesis was that, like dairy cows, goats and sheep are able to compensate for the missing nutritional supply of vitD through endogenous production in the skin, with the consequence of a high vitD status and a balanced Ca homeostasis. Sixteen lambs and 14 goat kids aged 3 and a half months were housed in an UVB free environment and fed hay and a vitD-free concentrate over a period of 13 wk. One group of each species was exposed to UVB lamps daily during individual feeding; the other groups served as controls. Serum, urine, and feces samples were taken at the start and at a monthly interval. Serum was analyzed for vitD metabolites, bone markers, growth hormone, insulin-like growth factor I, Ca, and P. Apparent digestibility and urinary excretion of Ca and P were determined. The left metatarsus was analyzed by peripheral quantitative computer tomography for bone mineral density before starting and at the end of the trial. In wk 13, all animals were slaughtered and samples of skin, rumen, duodenum, kidney, and bone (metatarsus) were collected. Content of sterols of vitD synthesis in the skin, Ca flux rates in rumen and duodenum, expression of vitD receptor in duodenum and kidney, renal and intestinal gene expression of Ca transport proteins, and renal enzymes related to vitD metabolism were determined. The UVB exposure led to lower 7-dehydrocholesterol content in the skin and a better vitD status (higher serum 25-hydroxyvitamin D), but no signs of vitD deficiency were seen in the control groups and no effect of irradiation was detected in the analyzed parameters of Ca homeostasis. Differences between the 2 species were detected: lambs had a higher increase of bone mineral density, lower values of bone markers, growth hormone, and insulin-like growth factor I in serum and higher tachysterol and lower lumisterol content in skin compared with goat kids. The results indicated that growing lambs and goat kids are able to compensate for a vitD-reduced diet by cutaneous vitD synthesis when exposed to UVB irradiation and therefore to keep a high vitD status. In contrast, when a reduced vitD diet is combined with missing UVB exposure, the vitD status drops, but the experimental time was probably too short to induce a vitD deficiency or an effect on Ca homeostasis.

A hyperparasite affects the population dynamics of a wild plant pathogen.

Assessing the impact of natural enemies of plant and animal pathogens on their host's population dynamics is needed to determine the role of hyperparasites in affecting disease dynamics, and their potential for use in efficient control strategies of pathogens. Here, we focus on the long-term study describing metapopulation dynamics of an obligate pathogen, the powdery mildew (Podosphaera plantaginis) naturally infecting its wild host plant (Plantago lanceolata) in the fragmented landscape of the Åland archipelago (southwest Finland). Regionally, the pathogen persists through a balance of extinctions and colonizations, yet factors affecting extinction rates remain poorly understood. Mycoparasites of the genus Ampelomyces appear as good candidates for testing the role of a hyperparasite, i.e. a parasite of other parasites, in the regulation of their fungal hosts' population dynamics. For this purpose, we first designed a quantitative PCR assay for detection of Ampelomyces spp. in field-collected samples. This newly developed molecular test was then applied to a large-scale sampling within the Åland archipelago, revealing that Ampelomyces is a widespread hyperparasite in this system, with high variability in prevalence among populations. We found that the hyperparasite was more common on leaves where multiple powdery mildew strains coexist, a pattern that may be attributed to differential exposure. Moreover, the prevalence of Ampelomyces at the plant level negatively affected the overwinter survival of its fungal host. We conclude that this hyperparasite may likely impact on its host population dynamics and argue for increased focus on the role of hyperparasites in disease dynamics.

Central venous oxygen saturation and carbon dioxide gap as resuscitation targets in a hemorrhagic shock.

BACKGROUND: Fluid resuscitation is still a major challenge. We aimed to describe changes in central venous oxygen saturation (ScvO2 ) and venous-to-arterial carbon dioxide gap (dCO2 ) during an experimental stroke volume (SV) index (SVI)-guided hemorrhage and fluid resuscitation model in pigs. METHODS: Twelve anesthetized, mechanically ventilated pigs were bled till baseline SVI (Tbsl ) dropped by 50% (T0 ), thereafter fluid resuscitation was performed with balanced crystalloid in four steps until initial SVI was reached (T4 ). Statistical analysis was performed with Statistical Program for Social Sciences version 18.0; data are expressed as mean ± standard deviation. RESULTS: After bleeding, ScvO2 dropped (Tbsl = 78 ± 7 vs. T0 = 61 ± 5% P < 0.05) and oxygen extraction ratio increased (Tbsl = 0.20 ± 0.07 vs. T0 = 0.36 ± 0.05, P < 0.05). By T4 the ScvO2 normalized, but on average it remained 5% lower than at Tbsl (T4 = 73 ± 9% P < 0.05) and oxygen extraction also remained higher as compared with Tbsl (T4 = 0.24 ± 0.09 P = 0.001). ScvO2 showed significant correlation with SVI (r = 0.564, P < 0.001). dCO2 increased during hypovolemia (Tbsl :5.3 ± 2.0 vs. T0 :9.6 ± 2.3 mmHg, P = 0.001), then returned to normal by T4 = 5.1 ± 2.6 mmHg, and it also showed significant correlation with SVI (R = -0.591, P < 0.001) and oxygen extraction (R = 0.735, P < 0.001). CONCLUSIONS: In this SV-guided bleeding and fluid resuscitation model, both ScvO2 and dCO2 correlated well with changes in SV, but only the dCO2 returned to its baseline, normal value, while ScvO2 remained significantly lower than at baseline. These results suggest that dCO2 may be a good hemodynamic endpoint of resuscitation, while ScvO2 is not strictly a hemodynamic parameter, but rather an indicator of the balance between oxygen delivery and consumption.

Performance and health of broiler chickens fed low erucic acid, lower fiber pennycress (CoverCressTM) grain.

CoverCress (low erucic acid, lower fiber pennycress) is being developed as a cover crop to be planted in the fall after corn and harvested in the spring prior to planting soybeans. Two experiments were conducted to evaluate 2 lines of the whole grain (CCWG-1: natural mutation and mutation breeding; CCWG-2: gene edited) and the whole grain pretreated with the potential palatability agent copper sulfate (CCWG-1-CuSO4; CCWG-2-CuSO4) as an ingredient for broilers. In Experiment 1, CCWG-1-CuSO4 was included in the diet at 0, 4, and 6% for 41 d. Feed intake, body weight gain, feed conversion, processing characteristics, organ weights, serum thyroid, macropathology and histology data were collected. In Experiment 2, broilers were fed diets containing Control, 2% CCWG-1, 4% CCWG-1, 4% CCWG-2, and 4.35% CCWG-1-CuSO4 for 42 d. Feed intake, body weight gain, feed conversion, organ weights, serum thyroid, blood chemistries, macropathology, and histology data were collected. In Experiment 1, feed intake and body weight were diminished with no effect on feed conversion for the birds consuming diets containing CCWG-1-CuSO4. In Experiment 2, feed intake and body weight were lower with no difference in feed conversion in birds fed diets containing greater than 2% CoverCress grain during d 0 to 28. During d 28 to 42 no difference in feed intake, body weight and an improvement in feed conversion was observed in birds fed all of the CoverCress grain products. In both experiments no significant negative effects were observed in processing, liver, kidney, and thyroid weights, T3, T4, blood chemistries, macropathology, and histopathology between the control and any of the CoverCress grain treatments. No difference in performance was observed in birds fed the mutant (4% CCWG-1) and gene-edited (4% CCWG-2) products. Pretreating CoverCress grain with copper sulfate did not have a significant effect on improving palatability. In conclusion, CoverCress grain can be safely fed to broilers when included at a target rate of 4% in diets and with total glucosinolate levels not to exceed 4.9 µmoles g-1.

HE4--a novel promising serum marker in the diagnosis of ovarian carcinoma.

Biomarkers have a wide range of applications in the management of several cancers. To date serum markers have been the most extensively used biomarkers in everyday practice but few markers are elevated in preclinical or premalignant disease, limiting their importance for estimating risk or for screening. Human epididymis protein-4 (HE4) is a novel serum marker which is more sensitive in the prediction of risk of ovarian malignancy than CA125 alone in patients with a pelvic mass. HE4 in combination with CA125 appears to be an effective tool for the early detection of recurrence or monitoring the response to therapy. Risk of Ovarian Malignancy Algorithm, utilizing the dual marker combination of HE4 and CA125, can be used to stratify both postmenopausal and premenopausal women into high- and low-risk groups, allowing for an effective triage of women to appropriate institutions for their care. A review of HE4 and its feasibility as a novel diagnostic tool in the management of epithelial ovarian cancer is presented.

Granular cell tumour of the breast: case series and review of the literature.

Granular cell tumours (GCTs) are uncommon rare neoplasms that may occur in any part of the body. Approximately 5-8% of granular cell tumours occur within the breast. Although nearly always benign in behaviour, granular cell tumours of the breast can often mimic breast malignancies both clinically and on the basis of imaging techniques. This article reports five cases of benign granular cell tumours appearing in the breast, mimicking a malignant breast lesion. In addition to reporting the cases, the relevant literature was reviewed.

The utility of delayed-enhancement magnetic resonance imaging for identifying nonischemic myocardial fibrosis in asymptomatic patients with biopsy-proven systemic sarcoidosis.

BACKGROUND: The pathophysiology of sarcoidosis includes infiltrative inflammatory injury, as well as interstitial fibrosis formation. Delayed-enhancement (DE) magnetic resonance imaging (MRI) techniques have been shown to identify fibrotic tissue as areas of hyperenhancement. To test the hypothesis that DE-MRI can be used to identify myocardial fibrosis resulting from cardiac sarcoidosis, we assessed this method in asymptomatic patients with biopsy-proven systemic sarcoidosis. METHODS: Thirty-one patients with biopsy-confirmed systemic sarcoidosis and no known history of heart disease or sarcoid cardiac involvement underwent DE-MRI after gadolinium-chelate administration. The location and extent of DE were quantified by 2 radiologists experienced at evaluating cardiovascular MRI images. RESULTS: According to DE-MRI, 8 (26%) of the 31 patients had nonischemic fibrosis, as evidenced by abnormal DE patterns. Unlike characteristic ischemic injuries, most of the fibrosis was mid-myocardial, extending to the adjacent endocardium, epicardium, or both. The most frequent site of fibrosis was the basal inferoseptum, followed by the basal inferolateral wall. CONCLUSIONS: In asymptomatic patients with systemic sarcoidosis, DE-MRI may provide a novel, noninvasive method for the early identification of myocardial fibrosis.

Comparison of broiler performance and carcass parameters when fed diets containing soybean meal produced from glyphosate-tolerant (MON 89788), control, or conventional reference soybeans.

A 42-d floor pen study was conducted to compare broiler (Ross x Ross 308) performance and carcass measurements when fed diets containing meal produced from glyphosate-tolerant soybeans (MON 89788) with those of broilers fed diets containing meal produced from control soybean (A3244) that has similar genetic background to MON 89788. Soybean meal produced from 6 conventional soybean varieties was included in the study to provide comparison measurements for broilers fed meal derived from conventional soybeans. It has been found that MON 89788 produces the 5-enolpyruvylshikimate-3-phosphate synthase protein from Agrobacterium sp. strain CP4 (cp4 epsps), which confers tolerance to glyphosate, the active ingredient in Roundup agricultural herbicides. Broilers were fed starter diets (approximately 33% wt/wt dehulled soybean meal) from d 0 to 21 and grower-finisher diets (approximately 30% wt/wt dehulled soybean meal) from d 21 to 42. The study utilized a randomized complete block design with 8 dietary treatments assigned randomly within 5 blocks of 16 pens each (8 male and 8 female) with 10 birds per pen. There were 10 pens per treatment group (5 male and 5 female). No treatment differences (P > 0.05) were detected among dietary treatments for feed intake, weight gain, adjusted feed conversion, or any measured carcass and meat quality parameters. Comparison of all performance, carcass, and meat quality parameters measured showed no differences (P > 0.05) between birds fed the MON 89788 soybean meal diet and the population of birds fed the control and 6 conventional reference soybean meal diets. It is concluded that the diets containing soybean meal produced from MON 89788 were nutritionally equivalent to diets containing soybean meal produced from the control and conventional reference soybean varieties when fed to broilers.

Comparison of broiler performance when fed diets containing grain from second-generation insect-protected and glyphosate-tolerant, conventional control or commercial reference corn.

Two 42-d floor pen studies were conducted to compare broiler (Ross x Ross 308) performance and carcass measurements when broilers were fed diets containing grain from either second-generation lepidopteran insect-protected corn (MON 89034; study 1) or second-generation lepidopteran combined with second-generation corn rootworm-protected and glyphosate-tolerant corn (MON 89034 x MON 88017; study 2) with those of diets containing corn grain from the conventional control and 4 conventional corn hybrids. In both studies, broilers were fed starter diets (approximately 55%, wt/wt, corn grain) from d 0 to 21 and grower-finisher diets (approximately 59%, wt/wt, corn grain) from d 21 to 42. Each study used a randomized complete block design with 6 dietary treatments assigned randomly within 5 blocks of 12 pens each (6 male and 6 female) and 10 pens per treatment group (5 male and 5 female). In study 1 (MON 89034), no treatment differences were detected among dietary treatments for feed intake, weight gain, or any measured carcass parameter. A significant difference was noted for adjusted feed conversion between MON 89034 and control birds; however, no differences were detected in individual treatment comparisons between the MON 89034 and 3 of the 4 commercial corn diets. In study 2 (MON 89034 x MON 88017), no treatment differences were observed for feed intake and most carcass parameters. When significant treatment differences were detected, no differences were observed between MON 89034 x MON 88017, its control, and 2 or more of the commercial corn diets. In each study, comparison of all parameters measured showed no differences between birds fed the test diet and the population of birds fed the control and 4 commercial corn diets. In conclusion, the test diets were nutritionally equivalent to diets containing the control and corn grain from commercial hybrids.

Comparison of broiler performance and carcass parameters when fed diets containing combined trait insect-protected and glyphosate-tolerant corn (MON 89034 x NK603), control, or conventional reference corn.

A 42-d floor pen study was conducted to compare broiler (Ross x Ross 308) performance and carcass measurements when fed diets containing lepidopteran-protected corn combined with glyphosate-tolerant corn (MON 89034 x NK603) with those of broilers fed diets containing corn grain from the conventional control (similar genetic background to the test corn) and 6 conventional corn hybrids. It has been found that MON 89034 produces the Cry1A.105 and Cry2Ab2 insecticidal proteins that protect corn plants from feeding damage caused by European corn borer (Ostrinia nubilalis) and other lepidopteran insect pests. In addition, NK603 produces the 5-enolpyruvylshikimate-3-phosphate synthase protein from Agrobacterium sp. strain CP4 (CP4 EPSPS), which confers tolerance to glyphosate, the active ingredient in Roundup agricultural herbicides. The traditional breeding of plants that express the individual traits produced MON 89034 x NK603. Broilers were fed starter diets (approximately 57% wt/wt corn grain) from d 0 to 21 and grower-finisher diets (approximately 59% wt/wt corn grain) from d 21 to 42. The study utilized a randomized complete block design with 8 dietary treatments assigned randomly within 5 blocks of 16 pens each (8 male and 8 female) with 10 birds per pen. There were 10 pens per treatment group (5 male and 5 female). Weight at d 0 and 42, feed intake, feed conversion, and all measured carcass and meat quality parameters were not different (P > 0.05) for birds fed MON 89034 x NK603 and control corn diets. In addition, comparisons of the MON 89034 x NK603 diet to the population of the control and 6 reference corn diets showed no difference (P > 0.05) in any performance, carcass, or meat quality parameter measured. In conclusion, the diets containing MON 89034 x NK603 were nutritionally equivalent to diets containing the control or conventional reference corn grain when fed to broilers.

Broiler performance and carcass characteristics when fed diets containing lysine maize (LY038 or LY038 x MON 810), control, or conventional reference maize.

Lysine maize (Zea mays), LY038, was developed through the application of modern biotechnology to accumulate free Lys in the germ portion of maize grain and provide an alternative to direct addition of supplemental Lys to poultry diets. Maize LY038 x MON 810 was produced by conventional breeding of LY038 with MON 810, which provides the corn plant protection against feeding damage from the European corn borer. A 42-d broiler feeding study (10 pens of 10 male Cobb x Cobb 500 broilers/treatment) was conducted to compare the feeding value of grain from LY038 or LY038 x MON 810 to that of a conventional control (similar genetic background to the test maize) and 5 conventional maize hybrids. The LY038 and LY038 x MON 810 maize-based diets and control and conventional reference maize-based diets supplemented with l-Lys HCl were formulated to a Lys level below that required for optimal bird performance, whereas all other essential amino acids were present at levels, relative to Lys, above those required for optimal bird performance [1.05% and 0.90% total Lys (as-fed) for d 0 to 21 and d 21 to 42, respectively]. Total Lys level in control and reference maize-based diets without supplemental l-Lys HCl was formulated to be 0.079% lower than supplemented diets. Weight gain, feed efficiency, and carcass yield and composition of broilers fed diets containing LY038 or LY038 x MON 810 were not different (P > 0.05) from that of broilers fed l-Lys HCl-supplemented diets and were superior (P < or = 0.05) to that of broilers fed conventional maize diets without supplemental l-Lys HCl. Both broiler performance and carcass data demonstrate that the bioefficacy of the incremental Lys in LY038 or LY038 x MON 810 grain was not different from that of Lys in conventional maize diets supplemented with l-Lys HCl. Thus, LY038 and LY038 x MON 810 can be considered as wholesome as and more nutritious than conventional maize due to its higher-than-average Lys content.

Results of a 90-day safety assurance study with rats fed grain from corn borer-protected corn.

The results of a 90-day rat feeding study with grain from MON 810 corn (YieldGard Cornborer -- YieldGard Cornborer is a registered trademark of Monsanto Technology, LLC) that is protected against feeding damage from corn and stalk boring lepidopteran insects are presented. Corn borer protection was accomplished through the introduction of cry1Ab coding sequences into the corn genome for in planta production of a bioactive form of Cry1Ab protein. Grain from MON 810 and its near-isogenic control was separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. (PMI). All diets were nutritionally balanced and conformed to PMI specifications for Certified LabDiet (PMI Certified LabDiet 5002 is a registered trademark of Purina Mills, Inc.) 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. The responses of rats fed diets containing MON 810 were compared to those of rats fed grain from conventional corn varieties. Overall health, body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, and gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 810 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 810 grain, confirming that it is as safe and nutritious as grain from existing commercial corn varieties.

Results of a 90-day safety assurance study with rats fed grain from corn rootworm-protected corn.

The results of a 90-day rat feeding study with YieldGard (YieldGard Rootworm Corn is a registered trademark of Monsanto Technology, LLC.) Rootworm corn (MON 863) grain that is protected against feeding damage caused by corn rootworm larvae are presented. Corn rootworm-protection was accomplished through the introduction of a cry3Bb1 coding sequence into the corn genome for in planta production of a modified Cry3Bb1 protein from Bacillus thuringiensis. Grain from MON 863 and its near isogenic control were separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. Additionally, six groups of rats were fed diets containing grain from different conventional (non-biotechnology-derived) reference varieties. The responses of rats fed diets containing MON 863 were compared to those of rats fed grain from conventional corn varieties. All diets were nutritionally balanced and conformed to Purina Mills, Inc. specifications for Certified LabDiet 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. Overall health, body weight gain, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 863 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 863 grain, confirming that it is as safe and nutritious as existing conventional corn varieties.

Comparison of broiler performance when fed diets containing corn grain with insect-protected (corn rootworm and European corn borer) and herbicide-tolerant (glyphosate) traits, control corn, or commercial reference corn.

A 42-d feeding experiment with growing Ross x Ross 508 broilers showed that the nutritional value of insect-protected and herbicide-tolerant corn was comparable to that of the genetically similar control and 5 commercial reference corn hybrids. MON 88017 provides protection from feeding damage by coleopteran pest corn rootworm and is tolerant to the action of glyphosate, the active ingredient in the Roundup family of agricultural herbicides. MON 88017 x MON 810 was developed by the traditional breeding of MON 88017 with MON 810, which provides protection from the European corn borer and other lepidopteran pests. A randomized complete block design was used with 8 dietary treatments in each of 5 replicated blocks of pens. No differences among diets were observed (P > 0.05) in performance (final live weights, feed intake, feed conversion, and adjusted feed conversion), carcass yield (chill, fat pad, breast, thigh, wing, and drum weight), or percentage of moisture, protein, and fat in breast meat and moisture and fat in thigh meat. Thigh protein was similar (P > 0.05) in broilers fed diets containing MON 88017 x MON 810 and conventional control or all commercial reference corns; however, differences (P < 0.05) were noted for the percentage of thigh protein among broilers fed the control and 2 of the 5 reference diets, attributable to biological variability among the conventional corn hybrids. Broilers overall performed consistently and had similar carcass yield and meat composition when fed diets containing MON 88017 or MON 88017 x MON 810 as compared with those fed the conventional control and commercial diets, supporting a conclusion of nutritional equivalence.

Comparison of broiler performance when fed diets containing corn grain with insect-protected (corn rootworm and European corn borer) and herbicide-tolerant (glyphosate) traits, control corn, or commercial reference corn--revisited.

A 42-d feeding experiment with growing Ross x Ross 508 broilers showed that the nutritional value of insect-protected and herbicide-tolerant corn was comparable to that of the genetically similar control and 5 commercial reference corn hybrids. MON 88017 provides protection from feeding damage by coleopteran pest corn rootworm and is tolerant to the action of glyphosate, the active ingredient in the Roundup family of agricultural herbicides. MON 88017 x MON 810 was developed by the traditional breeding of MON 88017 with MON 810, which provides protection from the European corn borer and other lepidopteran pests. A randomized complete block design was used with 8 dietary treatments in each of 5 replicated blocks of pens. No differences among diets were observed (P > 0.05) in performance (final live weights, feed intake, feed conversion, and adjusted feed conversion), carcass yield (chill, fat pad, breast, thigh, wing, and drum weight), or percentage of moisture, protein, and fat in breast meat and moisture and fat in thigh meat. Thigh protein was similar (P > 0.05) in broilers fed diets containing MON 88017 x MON 810 and conventional control or all commercial reference corns; however, differences (P < 0.05) were noted for the percentage of thigh protein among broilers fed the control and 2 of the 5 reference diets, attributable to biological variability among the conventional corn hybrids. Broilers overall performed consistently and had similar carcass yield and meat composition when fed diets containing MON 88017 or MON 88017 x MON 810 as compared with those fed the conventional control and commercial diets, supporting a conclusion of nutritional equivalence.

Short incubation with 7-oxo-prostacyclin induces long lasting prolongation of repolarisation time and effective refractory period in rabbit papillary muscle preparation.

STUDY OBJECTIVE - To determine whether the long lasting protection from early postocclusion and reperfusion arrhythmias induced by 7-oxo-prostacyclin is due to an anti-ischaemic effect alone or in combination with direct membrane effects. DESIGN - The study was performed on electrically stimulated isolated rabbit papillary muscle preparations with or without incubation with a stable prostacyclin analogue, 7-oxo-prostacyclinephedrine (7-oxo-PgI2). In some experiments, rabbits were pretreated with 7-oxo-PgI2. MEASUREMENTS and RESULTS - Marked prolongation of action potential duration (APD90) and effective refractory period developed 2 h after 20 min incubation with and subsequent washout of 7-oxo-PgI2, 1.1 X 10(-8) mol.litre-1. The same occurred if incubation with 7-oxo-PgI2 was maintained throughout the experiment. The only other change was a small diminution in amplitude of the action potential. During the 20 min incubation period neither APD90 nor effective refractory period was affected and only a transitory increase in the maximum rate of depolarisation, disappearing after washout, was seen. During the 4 h observation period there were no changes in the control preparations. The long lasting electrophysiological changes induced by 7-oxo-PgI2 were not affected by 60 min incubation with indomethacin, 2.8 X 10(-6) mol.litre-1. Pretreatment of rabbits with 7-oxo-PgI2, 50 micrograms.kg-1 intramuscularly, 48 h before the experiments prolonged effective refractory period v untreated controls. CONCLUSIONS - 7-oxo-PgI2 induces prolongation of APD90 and effective refractory period in adequately oxygenated normal papillary muscles as well as in ischaemic hearts. Therefore a direct membrane effect may contribute to its antiarrhythmic action, as well as an indirect anti-ischaemic effect. Such a direct effect is unlikely to be related to activation of the degradation products of the arachidonic acid cascade since it was not influenced by indomethacin.

The cellular electrophysiological effects of tedisamil in human atrial and ventricular fibers.

The cellular electrophysiological effects of 1 microM tedisamil (KC 8857) were studied in human atrial and ventricular fibers. Conventional microelectrode technique was applied to record the transmembrane action potentials at stimulation frequency of 100 per min and 37 degrees C. Tedisamil lengthened action potential duration (APD) more in atrial than in ventricular muscle fibers; prolongation of APD90 was 28.9 +/- 3.3% (n = 6; p < 0.05) for atrial and 13.3 +/- 5.2% (n = 6; P < 0.05) for ventricular tissue. The maximal rate of depolarization was depressed slightly, but significantly by 1 microM tedisamil only in ventricular fibers (12.9 +/- 6.5%, n = 6, P < 0.05). From these cellular electrophysiological data it is concluded that the bradycardic/antiischemic agent tedisamil possesses marked Class III properties not only in cardiac tissues of experimental animals but also those of man.

Solution assembly of the pseudo-high affinity and intermediate affinity interleukin-2 receptor complexes.

The high affinity interleukin-2 receptor is composed of three cell surface subunits, IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma. Functional forms of the IL-2 receptor exist, however, that enlist only two of the three subunits. On activated T-cells, the alpha- and beta-subunits combine as a preformed heterodimer (the pseudo-high affinity receptor) that serves to capture IL-2. On a subpopulation of natural killer cells, the beta- and gamma-subunits interact in a ligand-dependent manner to form the intermediate affinity receptor site. Previously, we have demonstrated the feasibility of employing coiled-coil molecular recognition for the solution assembly of a heteromeric IL-2 receptor complex. In that study, although the receptor was functional, the coiled-coil complex was a trimer rather than the desired heterodimer. We have now redesigned the hydrophobic heptad sequences of the coiled-coils to generate soluble forms of both the pseudo-high affinity and the intermediate affinity heterodimeric IL-2 receptors. The properties of these complexes were examined and their relevance to the physiological IL-2 receptor mechanism is discussed.

Estradiol and hemodynamics during ovulation induction.

Left ventricular size and stroke volume increase in human pregnancy and during estrogen administration in laboratory animals. In order to determine if elevated levels of endogenous estrogens in humans produce hemodynamic changes similar to those that occur during pregnancy, 14 patients were studied during ovulation induction at day 8 +/- 2 (SD) (proliferative phase) and at day 14 +/- 4 (midcycle) of their cycles. M-mode echocardiography was carried out with the patient in the left lateral decubitus, head down and head up positions. The mean serum estradiol level was 294 +/- 234 (SD) pg ml-1 at day 8 +/- 2 (treatment day) and it increased to 1503 +/- 531 pg ml-1 at day 14 +/- 4 (cycle day) of the same cycle. This change in serum estradiol was significant (P less than 0.001), associated with an increase in left ventricle diastolic dimension of 2.3 +/- 1.1 mm (P less than 0.001). During the same time period stroke volume and cardiac index correspondingly increased. Heart rate, fractional shortening, and blood pressure did not change and systemic vascular resistance decreased. Many of the cardiovascular adaptations of pregnancy are duplicated by high levels of endogenous estrogens and these changes are evident in as few as 6 days. Thus, we conclude that changes in endogenous estrogen correlate with certain cardiovascular parameters, the most striking of which is the left ventricular size. This may be one of the adaptive mechanisms by which the maternal circulation adapts to pregnancy.