Feeding value of supplemental curcas crude oil in finishing diets for feedlot lambs.

The objective of this experiment was to determine the feeding value of a mechanically extracted nontoxic variety of oil (JCO) as source of energy for feedlot lambs. Twenty Pelibuey × Katahdin lambs were individually fed a dry-rolled-corn-based finishing diet supplemented with 0%, 2%, 4%, or 6% JCO (diet dry matter basis). Supplemental JCO replaced dry rolled corn in the basal diet. Fatty acid composition of JCO was C16:0, 14.0%; C18:0, 8.2%; C18:1, 26.0%; C18:2, 50.3%, and C18:3, 0.4%. Daily intakes of JCO averaged 24.7, 51.1, and 77.3 g/day or 0.57, 1.08, and 1.62 g/kg LW for the 2%, 4%, and 6% levels of supplementation, respectively. Supplemental JCO did not affect ( = 0.33) dry matter intake (DMI), but tended to increase (linear effect, = 0.06) average daily gain, efficiency of gain (linear effect, < 0.01), and dietary net energy (linear effect, < 0.01) and decreased (linear effect, < 0.01) the ratio of observed/expected DMI. At low levels (20 g/kg diet dry matter) of supplementation, the net energy (NE) value of JCO corresponds closely (0.99) to the NE value assigned by current standards (), and this NE value decreased linearly as the inclusion level of JCO increased. There were not treatment effects on plasma metabolites. Across treatments, the concentrations of hemoglobin (11.64 ± 1.08 g/dL), hematocrit (39.15 ± 3.67%), glucose (85.2 ± 17.64 mg/dL), creatinine (1.43 ± 0.28 mg/dL), and urea (20.70 ± 4.35 mg/dL) were within normal (9-15 g/dL, 27%-40%, 50-90 mg/dL, 1.0-1.8 mg/dL, and 15-50 mg/dL, for hemoglobin, hematocrit, glucose, creatinine, and urea, respectively) ranges for healthy lambs. Based on DMI, performance and plasma metabolites observed in this study, nontoxic JCO is a suitable source of energy in finishing diets for lambs.

miR-300 mediates Bmi1 function and regulates differentiation in primitive cardiac progenitors.

B lymphoma Mo-MLV insertion region 1 (Bmi1) is a polycomb-family transcriptional factor critical for self-renewal in many adult stem cells and human neoplasia. We sought to identify microRNAs regulated by Bmi1 that could play a role in multipotent cardiac progenitor cell (CPC) decisions. We found that miR-300, a poorly characterized microRNA mapping in the Dlk1-Dio3 microRNA cluster, was positively regulated by Bmi1 in CPCs. Forced expression of miR-300 in CPCs promoted an improved stemness signature with a significant increase in Oct4 levels, a reduction in senescence progression and an enhanced proliferative status via p19 activation and inhibition of p16 accumulation. Endothelial and cardiogenic differentiation were clearly compromised by sustained miR-300 expression. Additionally, RNA and protein analysis revealed a significant reduction in key cardiac transcription factors, including Nkx2.5 and Tbx5. Collectively, these results suggest that some functions attributed to Bmi1 are due to induction of miR-300, which decreases the cardiogenic differentiation potential of multipotent CPCs in vitro and promotes self-renewal.

REPRODUCTIVE ACTIVITY AFTER INDUCED ANESTRUS USING ALTRENOGEST IN Tursiops truncatus FEMALES IN CAPTIVITY IN MARINE ENVIRONMENT / ACTIVIDAD REPRODUCTIVA DESPUÉS DEL ANESTRO INDUCIDO CON ALTRENOGEST EN HEMBRAS DE Tursiops truncatus EN CAUTIVERIO EN AMBIENTE MARINO

Interest to reproduce Bottlenose dolphin (Tursiops truncatus) in captivity has increased due to the international restrictions for its commercialization and the risks and logistical difficulties for transporting specimens. Therefore, it has become important to study its reproductive biology in captivity. The objective of the present study was to determine altrenogest (Regumate ®) post-treatment indicators of vaginal cytology, estradiol levels and restarting of reproductive activity of T truncatus females in captivity in marine environment. Twelve females received altrenogest at a daily dose of 0.07mg kg-1 for a year. A total 420 slides of vaginal cytology of each female were performed to determine the percentage of cornified cells. Also, 60 blood samples of each animal were analyzed to determine estradiol levels. Regarding the vaginal cytology; percentage of cornified cells increased between 60 and 70% from day 4 to day 9 after removing the altrenogest treatment and between 70 and 80% from day 12 to day 19. Estradiol levels were in the range of 16 to 1l4pg ml-1 during the entire monitoring period. A positive correlation (r = 0.7062; P<0.05) was found between these indicators. Therefore, we conclude that treatment with altrenogest and monitoring the estrous cycle with simple techniques such as vaginal cytology might be used for designing protocols for assisted reproduction for groups of T truncatus in captivity.

La necesidad de reproducir delfín nariz de botella (Tursiops truncatus) en cautiverio se ha incrementado debido a las restricciones internacionales para su comercialización y por el riesgo y dificultad logística para el traslado de ejemplares. Por lo anterior, se hace importante conocer su biología reproductiva en cautiverio. El objetivo de este trabajo, fue conocer los indicadores post tratamiento con altrenogest (Regumate®), de citología vaginal, niveles de estradiol y reinicio de la actividad reproductiva en cautiverio de hembras de T truncatus en ambiente marino. Por un año, 12 hembras recibieron diariamente una dosis de 0,07mg kg-1 de altrenogest. Se realizaron un total 420 citologías vaginales, una diaria de cada hembra, para determinar el porcentaje de células cornificadas. También se obtuvieron de la red vascular, 60 muestras sanguíneas, en las que se determinó los niveles de estradiol. En cuanto a la citología vaginal, al cuarto día de retirar la administración de altrenogest, el porcentaje total de células cornificadas incrementó del 60% a 70% hasta el día nueve y continuó ascendiendo al 80% entre los días 12 al 19. Los niveles de estradiol, presentaron un rango de 16 a 114pg ml-1. Se encontró una correlación (r = 0,7062 P<0.05) positiva entre estos indicadores. Se concluye que es posible la manipulación con altrenogest y el monitoreo del ciclo estral de las hembras mediante técnicas simples como la citología vaginal para el diseño de protocolos de reproducción asistida específicos para grupos en cautiverio de T truncatus.

Proliferative potential after DNA damage and non-homologous end joining are affected by loss of securin.

The faithful repair of DNA damage, especially chromosomal double-strand breaks (DSBs), is crucial for genomic integrity. We have previously shown that securin interacts with the Ku70/80 heterodimer of the DSB non-homologous DNA end-joining (NHEJ) repair machinery. Here we demonstrate that securin deficiency compromises cell survival and proliferation, but only after genotoxic stress. Securin(-/-) cells show a significant increase in gross chromosomal rearrangements and chromatid breaks after DNA damage, and also reveal an altered pattern of end resection in an NHEJ assay in comparison with securin(+/+) cells. These data suggest that securin has a key role in the maintenance of genomic stability after DNA damage, thereby providing a previously unknown mechanism for regulating tumour progression.

Enhancement of splenic-macrophage Fcgamma receptor expression by treatment with estrogens.

Splenic-macrophage Fcgamma receptors (FcgammaRs) participate in the pathophysiologies of immune-complex diseases and in host defense against infection. Modulation of macrophage FcgammaR expression is an immuno-therapeutic target. Glucocorticoids, sex steroids, and dopaminergic drugs modulate macrophage FcgammaR expression. Previous data indicate that estradiol increases macrophage FcgammaR expression. Nevertheless, the effects of clinically used estrogens upon macrophage FcgammaR expression are unknown. We assessed the effects of treatment with commonly used estrogens on the expression of macrophage FcgammaRs using a guinea pig experimental model. Six estrogens have been studied: ethynylestradiol (Et), mestranol (M), chlortianisene (Ct), promestriene, 17-epiestriol, and 17beta-estradiol. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic-macrophage FcgammaR cell surface expression. Estrogens enhance the clearance of IgG-sensitized erythrocytes by increasing splenic-macrophage FcgammaR expression. Et, M, and Ct were more effective than the other estrogens. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that estrogens increase the cell surface expression of FcgammaR1 and -2 more than that of FcgammaR2. These data indicate that treatment with commonly used estrogens enhances the clearance of IgG-sensitized cells by improving splenic-macrophage FcgammaR expression.

Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase.

We have previously isolated the hpttg proto-oncogene, which is expressed in normal tissues containing proliferating cells and in several kinds of tumors. In fact, expression of hPTTG correlates with cell proliferation in a cell cycle-dependent manner. Recently it was reported that PTTG is a vertebrate analog of the yeast securins Pds1 and Cut2, which are involved in sister chromatid separation. Here we show that hPTTG binds to Ku, the regulatory subunit of the DNA-dependent protein kinase (DNA-PK). hPTTG and Ku associate both in vitro and in vivo and the DNA-PK catalytic subunit phosphorylates hPTTG in vitro. Furthermore, DNA double-strand breaks prevent hPTTG-Ku association and disrupt the hPTTG-Ku complexes, indicating that genome damaging events, which result in the induction of pathways that activate DNA repair mechanisms and halt cell cycle progression, might inhibit hPTTG-Ku interaction in vivo. We propose that hPTTG might connect DNA damage-response pathways with sister chromatid separation, delaying the onset of mitosis while DNA repair occurs.

Effects of androgen treatment on expression of macrophage Fcgamma receptors.

Macrophage Fcgamma receptors (FcgammaRs) play an important role in the host defense against infection and in the pathophysiology of immune cytopenias. Modulation of macrophage FcgammaR expression is a potential therapeutic approach to immune disorders. Glucocorticoids and progesterones decrease macrophage FcgammaR expression. We assessed the effect of treatment with androgens and antiandrogens on the expression of macrophage FcgammaRs using an experimental guinea pig model. Four androgens (testosterone, dihydrotestosterone, mesterolone, and danazol) and five antiandrogens (flutamide, nilutamide, cyproterone acetate, spironolactone, and finasteride) were studied. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic macrophage FcgammaR cell surface expression. All of the androgens impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage FcgammaR expression. Dihydrotestosterone and mesterolone were more effective than testosterone or dihydrotestosterone. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that the androgens decreased the cell surface expression of FcgammaR1,2 more than that of FcgammaR2. Antiandrogens did not significantly alter macrophage FcgammaR expression. Nevertheless, antiandrogens counteracted the effects of androgens on macrophage FcgammaR expression. These data indicate that androgens impair the clearance of IgG-coated cells by decreasing splenic macrophage FcgammaR expression. Thus, androgens other than danazol are candidate drugs for the treatment of immune disorders.

Cardiopulmonary Rehabilitation, Exercise Training, and Preventive Cardiology: An Overview of a Decade of Research at the Ochsner Heart and Vascular Institute: Presented in part at Grand Rounds, Research Series, Ochsner Medical Institutions, May 17, 1999.

A decade of research from the Ochsner Heart and Vascular Institute's cardiopulmonary rehabilitation and exercise training programs demonstrates the benefits of this therapy on coronary risk factors, exercise capacity, cardiopulmonary parameters, behavioral characteristics, and quality of life in various subgroups of patients, including the elderly, women, obese patients, and groups with dyslipidemia and psychological distress, as well as in patients with congestive heart failure or severe lung disease. Substantial data from our program support the idea that cardiopulmonary rehabilitation and exercise training programs are underemphasized and underutilized for the secondary prevention of coronary artery disease.

Mitral inflow and pulmonary venous Doppler measurements do not predict pulmonary capillary wedge pressure in heart transplant recipients.

BACKGROUND: Noninvasive estimation of pulmonary capillary wedge pressure (PCWP) with Doppler-derived mitral inflow pattern has been shown to correlate well with invasively measured PCWP; however, it has not yet been determined whether Doppler-derived mitral inflow pattern can be used to estimate PCWP accurately in heart transplant recipients. METHODS: To determine if mitral and pulmonary venous inflow data can be applied to calculate PCWP in heart transplant recipients, some-day echocardiograms and right heart catheterizations were reviewed and 83 echocardiograms with adequate mitral inflow patterns in 53 patients were studied. Twenty-eight studies that also had adequate pulmonary venous inflow patterns were selected for offline analysis. RESULTS: Using a previously published formula [PCWP = 17 + (5.3 x E/A) - (0.11 x IVRT)], where E/A is the ratio of early to late mitral inflow velocities and IVRT is the isovolumic relaxation time, we derived a calculated PCWP, the results of which compared poorly with the measured PCWP (r = 0.33; p = 0.002). Linear regression analysis of measured PCWP versus mitral inflow Doppler flow velocity parameters also revealed poor to modest correlation. Adding parameters derived from the pulmonary venous inflow patterns failed to improve this correlation. CONCLUSION: Doppler-derived estimation of PCWP with mitral and pulmonary venous inflow patterns cannot be used to reliably predict PCWP in heart transplant recipients.

Type IIB von Willebrand's disease associated with a complex thrombocytopenic thrombocytopathy.

A familial bleeding disorder characterized by an association of Type IIB von Willebrand's disease (vWD) with a complex thrombocytopenic thrombocytopathy is described in two patients from the same generation. Findings typical of type IIB vWD included enhanced ristocetin-induced binding of patient von Willebrand factor (vWF) to platelets of patients and normal individuals in association with the absence of larger multimers from plasma. Abnormalities in platelet function included deficient platelet aggregation to ADP, collagen, epinephrine, and arachidonic acid; and defective release of 14C-serotonin, vWF, and platelet factor 4 (PF4) in response to thrombin, collagen, or ADP. Platelet factor 4 and platelet vWF were decreased when measured per mg of total platelet protein. In addition, the binding of normal vWF to patient platelets stimulated with thrombin was decreased. Platelet size was increased with a very heterogeneous distribution width. Electron microscopic evaluation showed giant platelets with dense and alpha bodies present. The platelet count was borderline or slightly decreased in the resting state and declined to frankly thrombocytopenic levels at the time of acute bleeding episodes; this state was associated with the presence of platelet aggregates in blood smears.