Inverse effects of activin and inhibin on the synthesis and secretion of FSH and LH by ovine pituitary cells in vitro

Little information is available on the effects of activin and inhibin on the synthesis and secretion of pituitary gonadotrophins in species other than the rat. In this in-vitro study, ovine pituitary cell cultures derived from immature sheep were used to investigate the effects of recombinant human activin-A and native Mr 32,000 bovine inhibin on basal and gonadotrophin-releasing hormone (GnRH)-induced release of FSH and LH. Residual cellular contents of FSH and LH were also determined, allowing total content/well to be calculated. Activin-A promoted a dose-dependent increase in basal (+72%; P less than 0.001) and GnRH-induced (+25%; P less than 0.001) release of FSH as well as in the residual cell content (+114%; P less than 0.001) and total FSH content/well (+67%; P less than 0.001). Conversely, inhibin significantly (P less than 0.001) suppressed each aspect of FSH production examined, confirming that in sheep, as in rats, activin and inhibin exert opposing effects on pituitary FSH production. In contrast to the rat, however, in which activin is reported to have no effect on LH secretion, exposure of sheep pituitary cells to activin-A promoted a dose-dependent suppression (-42%; P less than 0.001) of GnRH-induced LH release. This was associated with a corresponding increase (P less than 0.001) in residual cellular content of LH. Consistent with a previous report from this laboratory, inhibin had the opposite effect and significantly enhanced (+47%; P less than 0.001) GnRH-induced LH release. This was associated with a corresponding fall (P less than 0.01) in residual cellular content of LH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Emergency coronary artery stenting for coronary dissection complicating diagnostic cardiac catheterisation.

Dissection of a coronary artery is a recognised and significant complication of diagnostic coronary angiography that often requires emergency coronary artery bypass grafting. A coronary stent was used to treat this complication. This technique has potential advantages in terms of speed of reperfusion and availability in centres performing diagnostic angiography without surgical cover on site.     

Peroxynitrite formation and sinusoidal endothelial cell injury during acetaminophen-induced hepatotoxicity in mice

INTRODUCTION: Vascular injury and accumulation of red blood cells in the space of Disse (hemorrhage) is a characteristic feature of acetaminophen hepatotoxicity. However, the mechanism of nonparenchymal cell injury is unclear. Therefore, the objective was to investigate if either Kupffer cells or intracellular events in endothelial cells are responsible for the cell damage. RESULTS: Acetaminophen treatment (300 mg/kg) caused vascular nitrotyrosine staining within 1 h. Vascular injury (hemorrhage) occurred between 2 and 4 h. This paralleled the time course of parenchymal cell injury as shown by the increase in plasma alanine aminotransferase activities. Inactivation of Kupffer cells by gadolinium chloride (10 mg/kg) had no significant effect on vascular nitrotyrosine staining, hemorrhage or parenchymal cell injury. In contrast, treatment with allopurinol (100 mg/kg), which prevented mitochondrial injury in hepatocytes, strongly attenuated vascular nitrotyrosine staining and injury. CONCLUSIONS: Our data do not support the hypothesis that acetaminophen-induced superoxide release leading to vascular peroxynitrite formation and endothelial cell injury is caused by activated Kupffer cells. In contrast, the protective effect of allopurinol treatment suggests that, similar to the mechanism in parenchymal cells, mitochondrial oxidant stress and peroxynitrite formation in sinusoidal endothelial cells may be critical for vascular injury after acetaminophen overdose.     

Production of insulin-like growth factors by ovarian granulosa cells

Evidence for ovarian secretion of somatomedins or insulin-like growth factors (IGF's) was generated by two approaches. First, porcine granulosa cells were shown to produce IGF's and an IGF-binding protein under serum-free conditions in vitro. The ovarian IGF's were recognized in two competitive binding assays specific for IGF's, a RIA using antibodies to human IGF-I and a radioreceptor assay using rat liver plasma membranes. IGF secretion was maintained for at least 10 days in culture. Second, ovarian production of IGF's in vivo was suggested by studies which showed that IGF levels in follicular fluid from preovulatory follicles were significantly greater than those in either serum or immature follicles. In contrast, similar low levels of insulin were observed in the follicles and serum. In conjunction with previous evidence of IGF action on granulosa cells, the present studies suggest the possibility of an autocrine role of IGF's in regulating follicular growth and development.     

Renal impairment and anaemia in a population-based study of older people

Abstract
Background: Established renal failure is a known cause of anaemia. However, the association between more modest levels of renal impairment and anaemia is unclear.
Aims: The aim of the present study was to investigate the association between mild renal impairment and anaemia in the general population.
Methods: A population-based, cross-sectional study was conducted in the general community in an urban area of the Blue Mountains, just west of Sydney, Australia. The study included 3222 people aged ≥49 years (mean age 65 years). Serum creatinine and haemoglobin were measured using standard laboratory techniques. Creatinine clearance was estimated from serum creatinine, body weight, sex and age.
Results:  Two hundred and seventy subjects (8.4%) had serum creatinine levels ≥125 µmol/L and estimated ­creatinine clearances were <0.84 mL/s (50 mL/min) in 894 subjects (27.7%) and <0.50 mL/s (30 mL/min) in 120 subjects (3.7%). There was a strong association between reduced renal function and anaemia. Compared to those with serum creatinine <125 µmol/L, the age-adjusted relative risk (RR) of anaemia in women (haemoglobin <12.0 g/dL) with serum creatinine ≥125 µmol/L was 5.5 (95% confidence interval (CI) 2.9−10.7) and the RR of anaemia in men (haemoglobin < 13.0 g/dL) was 3.1 (95% CI 1.6−6.0). Estimated ­creatinine clearance <50 mL/min was associated with a three-fold increased risk of anaemia in women and a five-fold increased risk in men.
Conclusions: The results of the present study suggest that even modestly impaired renal function is associated with anaemia in older men and women. The possibility of renal impairment should be considered in the diagnosis and management of anaemia in people aged>50 years. (Intern Med J 2004; 34: 20−23)     

Bilateral versus unilateral botulinum toxin injections for chronic anal fissure: a randomised trial

Background

Botulinum toxin injected into the internal anal sphincter is used in the treatment of chronic anal fissure but there is no standardised technique for its administration. This randomised single centre trial compares bilateral (either side of fissure) to unilateral injection.

Methods

Participants were randomised to receive bilateral (50?+?50 units) or unilateral (100 units) Dysport^® injections into the internal anal sphincter in an outpatient setting. Injection-related pain assessed by visual analogue scale was the primary outcome measure. Secondary outcomes were healing rate, fissure pain, incontinence, and global health scores.

Results

Between October 2008 and April 2012, 100 patients with chronic anal fissure were randomised to receive bilateral or unilateral injections. Injection-related pain was comparable in both groups. There was no difference in healing rate. Initially, there was greater improvement in fissure pain in the bilateral group but at 1 year the unilateral group showed greater improvement. Cleveland Clinic Incontinence score was lower in the unilateral group in the early post-treatment period and global health assessment (EuroQol EQ-VAS) was higher in the unilateral group at 1 year.

Conclusions

Injection-related pain was similar in bilateral and unilateral injection groups. Unilateral injection was as effective as bilateral injections in healing and improving fissure pain without any deterioration in continence.

     

Toward resolution of the debate regarding purported crypto-Jews in a Spanish-American population: Evidence from the Y chromosome

Background: The ethnic heritage of northernmost New Spain, including present-day northern New Mexico and southernmost Colorado, USA, is intensely debated. Local Spanish-American folkways and anecdotal narratives led to claims that the region was colonized primarily by secret- or crypto-Jews. Despite ethnographic criticisms, the notion of substantial crypto-Jewish ancestry among Spanish-Americans persists. Aim: We tested the null hypothesis that Spanish-Americans of northern New Mexico carry essentially the same profile of paternally inherited DNA variation as the peoples of Iberia, and the relevant alternative hypothesis that the sampled Spanish-Americans possess inherited DNA variation that reflects Jewish ancestry significantly greater than that in present-day Iberia. Subjects and Methods: We report frequencies of 19 Y-chromosome unique event polymorphism (UEP) biallelic markers for 139 men from across northern New Mexico and southern Colorado, USA, who self-identify as ‘Spanish-American’. We used three different statistical tests of differentiation to compare frequencies of major UEP-defined clades or haplogroups with published data for Iberians, Jews, and other Mediterranean populations. We also report frequencies of derived UEP markers within each major haplogroup, compared with published data for relevant populations. Results: All tests of differentiation showed that, for frequencies of the major UEP-defined clades, Spanish-Americans and Iberians are statistically indistinguishable. All other pairwise comparisons, including between Spanish-Americans and Jews, and Iberians and Jews, revealed highly significant differences in UEP frequencies. Conclusion: Our results indicate that paternal genetic inheritance of Spanish-Americans is indistinguishable from that of Iberians and refute the popular and widely publicized scenario of significant crypto-Jewish ancestry of the Spanish-American population.

Résumé. Arrière plan:?L’héritage ethnique de la partie la plus septentrionale de la Nouvelle Espagne, incluant aux USA l’actuel nord du Nouveau-Mexique et le sud du Colorado, est intensément discuté. Des traditions hispano-américaines locales et des anecdotes tendent à proclamer que cette région a été colonisée primitivement par des crypto-juifs. En dépit de critiques ethnographiques, la notion d’ancestralité substantielle crypto-juive persiste chez les hispano-américains.

But:?Tester l‘hypothèse nulle que les hispano-américains du Nouveau-Mexique septentrional présentent essentiellement le même profil de variation d’ADN paternel que les populations de la péninsule ibérique et l’hypothèse alternative que les hispano-américains échantillonnés possèdent une variation d’ADN qui reflète significativement plus l’ancestralité juive que l’ibérique.

Sujets et méthodes:?On reporte les fréquences de 19 polymorphismes uniques du chromosome Y (PU-Y) de marqueurs bi-alléliques chez 139 hommes du nord du Nouveau-Mexique et du sud du Colorado qui s’auto-identifient comme hispano-américains. On utilise trois tests statistiques de différenciation afin de comparer les fréquences des clades ou haplogroupes de PU-Y majeurs, ainsi que les fréquences des marqueurs PU-Y singularisés à l’intérieur de chaque haplogroupe majeur, avec les données publiées pour les espagnols, les juifs et d’autres populations méditerranéennes.

Résultats:?Tous les tests de différenciation montrent que les hispano-américains et les ibères sont statistiquement indistincts pour les fréquences des clades majeurs à définition PU-Y. Toutes les autres comparaisons deux à deux incluant hispano-américains et juifs et ibères et juifs, montrent des différences hautement significatives des fréquences PU-Y.

Conclusion: Nos résultats indiquent que l’hérédité paternel des hispano-américains ne peut être distinguée de celle des ibères et réfute le scénario populaire et largement diffusé, de l’existence d’une origine significative crypto-juive de la population hispano-américaine.

Zusammenfassung. Hintergrund:?Das ethnische Erbe des nördlichsten Teils von Neuspanien, einschliess;lich des heutigen New Mexico und des südlichen Colorado, USA, unterliegt intensiven Diskussionen. Lokale spanisch-amerikanische Traditionen und Anekdoten haben zu Behauptungen beigetragen, dass diese Region hauptsächlich von Geheimjuden beziehungsweise sogenannten crypto-jews kolonialisiert worden war. Trotz ethnographischer Kritik an dieser Theorie, hält sich die Vorstellung, dass ein bedeutender Anteil der heutigen in dieser Region lebenden Spanisch-Amerikaner von crypto-Jewish Vorfahren abstammen.

Ziel:?Wir untersuchen die Nullhypothese, die besagt, dass die Spanisch-Amerikaner des nördlichen New Mexico im Wesentlichen dasselbe Profil väterlich vererbter DNS-Variationen zeigen wie die Bevälkerung der Iberischen Halbinsel, und die entsprechende Alternativhypothese, die besagt, dass die getesteten Spanisch-Amerikaner DNS-Variationen besitzen, die ein signifikant höheres Mass; an jüdischer Herkunft widerspiegelen als die, die heute auf der Iberischen Halbinsel vorgefunden werden.

Probanden und Methoden:?Für 139 Männer aus dem nördlichen New Mexico und südlichen Colorado, USA, die sich selbst als, Spanisch-Amerikaner“ bezeichnen, wurde eine Genotypisierung auf dem Y-Chromosom anhand von 19 verschiedenen biallelischen Markern (unique event polymorphism, UEP) vorgenommen. Drei verschiedene statistische Tests wurden ausgeführt, um mögliche Unterschiede bei den Häufigkeiten der wesentlichen UEP-definierten Stämme oder Haplogruppen mit denen von bisher veröffentlichten Daten von Bewohnern der Iberischen Halbinsel, Juden sowie anderen mediterranen Völkern vergleichen zu können. Auss;erdem berichten wir die Häufigkeiten von abgeleiteten UEP-Markern innerhalb einer jeden Haupt-Haplogruppe und vergleichen diese mit publizierten Daten für die entsprechenden Populationen.

Ergebnisse:?Alle Untersuchungen auf Unterschiede zeigten für die Häufigkeiten der wesentlichen UEP-definierten Stämme, dass sich die der Spanisch-Amerikaner und der Bewohner der Iberischen Halbinsel statistisch nicht unterscheiden. Alle anderen paarweisen Vergleiche, einschliess;lich derer zwischen zum einen Spanisch-Amerikanern und Juden und zum anderen Bewohnern der Iberischen Halbinsel und Juden, zeigten signifikante Unterschiede in den jeweiligen UEP-Häufigkeiten.

Zusammenfassung:?Unsere Ergebnisse legen nahe, dass die väterliche genetische Vererbung bei Spanisch-Amerikanern nicht von der der iberischen Bevölkerung zu unterscheiden ist. Das populäre und oft publizierte Szenario einer signifikanten crypto-Jewish Abstammung, unter der heutigen spanisch-amerikanischen Bevölkerung wird damit widerlegt.

Resumen. Antecedentes:?La herencia étnica de la Nueva España situada más al norte, que incluye el norte del actual Nuevo México y el sur de Colorado, E.E.U.U., es objeto de un intenso debate. El modo de vida y las narraciones anecdóticas locales hispanoamericanas conducen a afirmar que la región fue colonizada inicialmente por judíos secretos o cripto-judíos. A pesar de las críticas etnográficas, persiste aún la noción de una ascendencia cripto-judía substancial entre los hispanoamericanos.

Objetivo:?Comprobamos la hipótesis nula de que los hispano-americanos del norte de Nuevo México portan esencialmente el mismo perfil de variación de ADN heredada por vía paterna que los pueblos de la Península Ibérica, así como la hipótesis alternativa relevante de que los hispanoamericanos estudiados poseen una variación de ADN heredada que refleja su ascendencia judía de forma mucho más perceptible que en la actual Península Ibérica.

Sujetos y métodos:?Presentamos las frecuencias de 19 marcadores bialélicos de polimorfismo de evento único (UEP) del cromosoma Y, de 139 varones procedentes de la zona situada entre el norte de Nuevo México y el sur de Colorado (E.E.U.U.), quienes se identifican a sí mismos como “hispanoamericanos”. Utilizamos tres pruebas estadísticas distintas de diferenciación para comparar las frecuencias de los principales clados o haplogrupos de UEP, definidos mediante datos publicados sobre ibéricos, judíos y otras poblaciones mediterráneas. También presentamos las frecuencias derivadas de los marcadores UEP dentro de cada haplogrupo principal, comparadas con los datos publicados sobre poblaciones relevantes.

Resultados:?todos los tests de diferenciación mostraron que, para las frecuencias de los principales clados de UEP definidos, hispanoamericanos e ibéricos son estadísticamente indistinguibles. El resto de pares comparados, incluyendo hispanoamericanos y judíos, e ibéricos y judíos, revelaron diferencias altamente significativas en las frecuencias de los UEP.

Conclusión:?nuestros resultados indican que la herencia genética paterna de los hispanoamericanos es indistinguible de la de los ibéricos y refuta el escenario popular y ampliamente publicitado de una significativa ascendencia cripto-judía de la población hispanoamericana.     

Frontotemporal Regulation of Subjective Value to Suppress Impulsivity in Intertemporal Choices

Impulsive decisions arise from preferring smaller but sooner rewards compared with larger but later rewards. How neural activity and attention to choice alternatives contribute to reward decisions during temporal discounting is not clear. Here we probed (1) attention to and (2) neural representation of delay and reward information in humans (both sexes) engaged in choices. We studied behavioral and frequency-specific dynamics supporting impulsive decisions on a fine-grained temporal scale using eye tracking and MEG recordings. In one condition, participants had to decide for themselves but pretended to decide for their best friend in a second prosocial condition, which required perspective taking. Hence, conditions varied in the value for themselves versus that pretending to choose for another person. Stronger impulsivity was reliably found across three independent groups for prosocial decisions. Eye tracking revealed a systematic shift of attention from the delay to the reward information and differences in eye tracking between conditions predicted differences in discounting. High-frequency activity (175-250 Hz) distributed over right frontotemporal sensors correlated with delay and reward information in consecutive temporal intervals for high value decisions for oneself but not the friend. Collectively, the results imply that the high-frequency activity recorded over frontotemporal MEG sensors plays a critical role in choice option integration.SIGNIFICANCE STATEMENT Humans face decisions between sooner smaller rewards and larger later rewards daily. An objective benefit of losing weight over a longer time might be devalued in face of ice cream because they prefer currently available options because of insufficiently considering long-term alternatives. The degree of contribution of neural representation and attention to choice alternatives is not clear. We investigated correlates of such decisions in participants deciding for themselves or pretending to choose for a friend. Behaviorally participants discounted less in self-choices compared with the prosocial condition. Eye movement and MEG recordings revealed how participants represent choice options most evident for options with high subjective value. These results advance our understanding of neural mechanisms underlying decision-making in humans.