Clinical and Pathological Features of Pheochromocytoma in the Horse: A Multi-Center Retrospective Study of 37 Cases (2007-2014).

BACKGROUND: Pheochromocytoma is the most common adrenal medullary neoplasm of domestic animals, but it is rare in horses. Antemortem diagnosis in horses is difficult, with clinical signs often being vague or non-specific. OBJECTIVE: The objective of this study was to describe the clinical, laboratory, and pathologic findings of pheochromocytoma in horses. ANIMALS: Thirty-seven horses diagnosed with pheochromocytoma based on postmortem examination from 2007 to 2014. METHODS: Retrospective case series. RESULTS: Pheochromocytoma was identified in 37/4094 horses during postmortem examination. Clinical signs consistent with pheochromocytoma had been observed antemortem in only 7 cases, with the remainder being incidental findings. Colic was the most common presenting complaint (13 of 37 cases) and tachycardia was noted in 95% of cases (median heart rate of 86 bpm in clinical cases). Hyperlactatemia (median, 4.9 mmol/L) and hyperglycemia (median, 184 mg/dL) were the most common clinicopathologic abnormalities. Hemoperitoneum caused by rupture of pheochromocytoma was noted in 4/7 clinical cases. Concurrent endocrine abnormalities (eg, thyroid adenoma, adrenal hyperplasia, pituitary pars intermedia hyperplasia or adenoma, parathyroid C-cell carcinoma) were found in 27/37 horses, with 8/37 horses having lesions consistent with multiple endocrine neoplasia syndrome as described in humans. CONCLUSIONS: Pheochromocytoma was diagnosed in 0.95% of horses presented for necropsy. The majority of these were incidental findings, but pheochromocytoma was thought to contribute to clinical findings in 19% of cases, and multiple endocrine neoplasms were commonly seen. Usually an incidental finding at necropsy, pheochromocytoma may cause acute death from intraperitoneal exsanguination and should be considered in horses presenting with colic, tachycardia, and hemoperitoneum.

Research in animal reproduction: Quo vadimus?

Population growth and trends in food consumption are expected to result in a net food deficit and widespread loss of food security across the globe within four decades. It is generally accepted that this crisis will have to be met by increased livestock production, using less land, less water and in an environmentally sustainable fashion. As animal reproduction and reproductive efficiency are the basis of livestock production, it is essential that technological advances be made to increa se the animal-based food supply. Improvements are required in artificial insemination procedures, in embryo transfer and in transgenic animal production. Technology is evolving such that it may soon be possible to rapidly sequence genomes and transcriptomes to hasten genetic improvements, to produce gametes from stem cells, and to increase success rates in livestock transgenesis. The principal constraints at this time are on research funding and on the paucity of scientists with multidisciplinary skills. Given its livestock population, its biodiversity, and its burgeoning scientif ic expertise, Brazil is expected to be a major contributor to the resolution of food security problems in coming years.

Equine chorionic gonadotropin: an enigmatic but essential tool

Equine chorionic gonadotropin (eCG) was discovered more than 80 y ago as a factor found in circulation of the pregnant mare during the first third of gestation. It is a variant of equine luteinizing hormone (LH), differentially glycosylated by the equine trophoblast cells. It has the peculiar property of provoking both follicle-stimulating hormone (FSH) and LH activity in non-equid species. The biological basis for this dual activity is believed to be the result of promiscuity of the mammalian FSH receptors, imparting the capacity to respond to this equine LH-like hormone. The best approximation of the role of eCG in the mare is that it induces accessory corpora lutea to better support early gestation. There are numerous applications for eCG in domestic species, including induction of puberty, reversal of anestrus, superovulation and, most recently, improvement of fertility.

Equine chorionic gonadotropin: an enigmatic but essential tool

Equine chorionic gonadotropin (eCG) was discovered more than 80 y ago as a factor found in circulation of the pregnant mare during the first third of gestation. It is a variant of equine luteinizing hormone (LH), differentially glycosylated by the equine trophoblast cells. It has the peculiar property of provoking both follicle-stimulating hormone (FSH) and LH activity in non-equid species. The biological basis for this dual activity is believed to be the result of promiscuity of the mammalian FSH receptors, imparting the capacity to respond to this equine LH-like hormone. The best approximation of the role of eCG in the mare is that it induces accessory corpora lutea to better support early gestation. There are numerous applications for eCG in domestic species, including induction of puberty, reversal of anestrus, superovulation and, most recently, improvement of fertility.(AU)

Research in animal reproduction: Quo vadimus?

Population growth and trends in food consumption are expected to result in a net food deficit and widespread loss of food security across the globe within four decades. It is generally accepted that this crisis will have to be met by increased livestock production, using less land, less water and in an environmentally sustainable fashion. As animal reproduction and reproductive efficiency are the basis of livestock production, it is essential that technological advances be made to increa se the animal-based food supply. Improvements are required in artificial insemination procedures, in embryo transfer and in transgenic animal production. Technology is evolving such that it may soon be possible to rapidly sequence genomes and transcriptomes to hasten genetic improvements, to produce gametes from stem cells, and to increase success rates in livestock transgenesis. The principal constraints at this time are on research funding and on the paucity of scientists with multidisciplinary skills. Given its livestock population, its biodiversity, and its burgeoning scientif ic expertise, Brazil is expected to be a major contributor to the resolution of food security problems in coming years.(AU)

The metabolic dynamics of cartilage explants over a long-term culture period.

INTRODUCTION: Although previous studies have been performed on cartilage explant cultures, the generalized dynamics of cartilage metabolism after extraction from the host are still poorly understood due to differences in the experimental setups across studies, which in turn prevent building a complete picture. METHODS: In this study, we investigated the response of cartilage to the trauma sustained during extraction and determined the time needed for the cartilage to stabilize. Explants were extracted aseptically from bovine metacarpal-phalangeal joints and cultured for up to 17 days. RESULTS: The cell viability, cell number, proteoglycan content, and collagen content of the harvested explants were analyzed at 0, 2, 10, and 17 days after explantation. A high percentage of the cartilage explants were found to be viable. The cell density initially increased significantly but stabilized after two days. The proteoglycan content decreased gradually over time, but it did not decrease to a significant level due to leakage through the distorted peripheral collagen network and into the bathing medium. The collagen content remained stable for most of the culture period until it dropped abruptly on day 17. CONCLUSION: Overall, the tested cartilage explants were sustainable over long-term culture. They were most stable from day 2 to day 10. The degradation of the collagen on day 17 did not reach diseased levels, but it indicated the potential of the cultures to develop into degenerated cartilage. These findings have implications for the application of cartilage explants in pathophysiological fields.

The metabolic dynamics of cartilage explants over a long-term culture period

INTRODUCTION: Although previous studies have been performed on cartilage explant cultures, the generalized dynamics of cartilage metabolism after extraction from the host are still poorly understood due to differences in the experimental setups across studies, which in turn prevent building a complete picture. METHODS: In this study, we investigated the response of cartilage to the trauma sustained during extraction and determined the time needed for the cartilage to stabilize. Explants were extracted aseptically from bovine metacarpal-phalangeal joints and cultured for up to 17 days. RESULTS: The cell viability, cell number, proteoglycan content, and collagen content of the harvested explants were analyzed at 0, 2, 10, and 17 days after explantation. A high percentage of the cartilage explants were found to be viable. The cell density initially increased significantly but stabilized after two days. The proteoglycan content decreased gradually over time, but it did not decrease to a significant level due to leakage through the distorted peripheral collagen network and into the bathing medium. The collagen content remained stable for most of the culture period until it dropped abruptly on day 17. CONCLUSION: Overall, the tested cartilage explants were sustainable over long-term culture. They were most stable from day 2 to day 10. The degradation of the collagen on day 17 did not reach diseased levels, but it indicated the potential of the cultures to develop into degenerated cartilage. These findings have implications for the application of cartilage explants in pathophysiological fields.

Epigenetic anomalies associated with prenatal survival and neonatal morbidity in cloned calves

Many of the developmental anomalies observed in cloned animals are related to fetal and placental overgrowth, a phenomenon known as the “large offspring syndrome” (LOS) in ruminants. It has been hypothesized that the epigenetic control of imprinted genes, i.e. genes that are expressed in a parental-specific manner, is at the root of LOS. Our recent research has focused on understanding the epigenetic alterations to imprinted genes that are associated with assisted reproductive technologies (ART), such as early embryo in vitro culture (IVC) and somatic cell nuclear transfer (SCNT) in cattle. We have searched and identified single nucleotide polymorphisms in Bos indicus DNA useful for analysis of parental-specific alleles and their respective transcripts in tissues from hybrid embryos derived by crossing Bos indicus and Bos taurus cattle. Due to the frequency of placental anomalies in SCNT and in some IVC gestations, our initial studies focused on genes known to be necessary for trophoblast proliferation (Mammalian Achaete Scute-like Homologue 2; ASCL2) and differentiation (Heart and neural crest cell derivative 1; HAND1). ASCL2 was bi-allelically expressed prior to implantation but paternally silenced after implantation. At day 17, SCNT embryos showed more abundant ASCL2 and less abundant HAND1 transcripts. After implantation, SCNT fetal cotyledons displayed higher ASCL2 and HAND1 than AI and IVC tissues. To further investigate epigenetic anomalies, we analyzed the differentially methylated regions of other imprinted genes in cattle, i.e. SNRPN, H19 and the IGF2R. Compared with the patterns observed in vivo (AI), we observed a generalized hypomethylation of the imprinted allele and the bi-allelic expression of embryos produced by SCNT...

Orphan nuclear receptor regulation of reproduction

Orphan nuclear receptors, those without known ligands, were discovered because of their structural similarity to the ligand-driven steroid and thyroid receptors. Since their characterization, many of the orphan receptors have been adopted, i.e., ligands, usually lipids or derived lipids, have been discovered. The orphan receptors are transcriptional regulators, functioning in the reproductive context to upregulate or suppress gene expression. By this means, the orphan receptors regulate a plethora of reproductive events. In the majority of cases, the effects are stimulatory, indeed, members of the NR2 family promote Leydig cell differentiation and testicular steroidogenesis, while those of the NR4 family regulate early gestation and placental formation. The NR5 family has two members, steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homolog-1 (LRH-1, NR5A2). These receptors interact with the same DNA sequence and are believed to be constitutive transcription factors. Their effects are modulated by the repressive effects of the NR0 family of orphan receptors that comprise the short heterodimeric partner (SHP, NR0B2) and dosage-sensitive sex reversal adrenal hypoplasia congenital region on the X chromosome, gene 1 (DAX1, NROB1). SHP and DAX1 inhibit the interaction of LRH-1 and SF-1 with coactivators, thereby reducing their constitutive transcriptional effects. Overall, the orphan nuclear receptors are essential regulators of reproductive function in mammals.

Orphan nuclear receptor regulation of reproduction

Orphan nuclear receptors, those without known ligands, were discovered because of their structural similarity to the ligand-driven steroid and thyroid receptors. Since their characterization, many of the orphan receptors have been adopted, i.e., ligands, usually lipids or derived lipids, have been discovered. The orphan receptors are transcriptional regulators, functioning in the reproductive context to upregulate or suppress gene expression. By this means, the orphan receptors regulate a plethora of reproductive events. In the majority of cases, the effects are stimulatory, indeed, members of the NR2 family promote Leydig cell differentiation and testicular steroidogenesis, while those of the NR4 family regulate early gestation and placental formation. The NR5 family has two members, steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homolog-1 (LRH-1, NR5A2). These receptors interact with the same DNA sequence and are believed to be constitutive transcription factors. Their effects are modulated by the repressive effects of the NR0 family of orphan receptors that comprise the short heterodimeric partner (SHP, NR0B2) and dosage-sensitive sex reversal adrenal hypoplasia congenital region on the X chromosome, gene 1 (DAX1, NROB1). SHP and DAX1 inhibit the interaction of LRH-1 and SF-1 with coactivators, thereby reducing their constitutive transcriptional effects. Overall, the orphan nuclear receptors are essential regulators of reproductive function in mammals.(AU)

Epigenetic anomalies associated with prenatal survival and neonatal morbidity in cloned calves

Many of the developmental anomalies observed in cloned animals are related to fetal and placental overgrowth, a phenomenon known as the “large offspring syndrome” (LOS) in ruminants. It has been hypothesized that the epigenetic control of imprinted genes, i.e. genes that are expressed in a parental-specific manner, is at the root of LOS. Our recent research has focused on understanding the epigenetic alterations to imprinted genes that are associated with assisted reproductive technologies (ART), such as early embryo in vitro culture (IVC) and somatic cell nuclear transfer (SCNT) in cattle. We have searched and identified single nucleotide polymorphisms in Bos indicus DNA useful for analysis of parental-specific alleles and their respective transcripts in tissues from hybrid embryos derived by crossing Bos indicus and Bos taurus cattle. Due to the frequency of placental anomalies in SCNT and in some IVC gestations, our initial studies focused on genes known to be necessary for trophoblast proliferation (Mammalian Achaete Scute-like Homologue 2; ASCL2) and differentiation (Heart and neural crest cell derivative 1; HAND1). ASCL2 was bi-allelically expressed prior to implantation but paternally silenced after implantation. At day 17, SCNT embryos showed more abundant ASCL2 and less abundant HAND1 transcripts. After implantation, SCNT fetal cotyledons displayed higher ASCL2 and HAND1 than AI and IVC tissues. To further investigate epigenetic anomalies, we analyzed the differentially methylated regions of other imprinted genes in cattle, i.e. SNRPN, H19 and the IGF2R. Compared with the patterns observed in vivo (AI), we observed a generalized hypomethylation of the imprinted allele and the bi-allelic expression of embryos produced by SCNT...(AU)

Resistencias nasales de referencia para rinomanometría anterior con máscara / Nasal resistances of reference for anterior rhimomanometry with mask

Se realizó un estudio del comportamiento de la resistencia nasal total y uninasal en reposo para inspiración y espiración en dos grupos de edad, utilizando un rinomanómetro equipado con máscara para las mediciones y el modelo matemático de Broms para el análisis de las curvas de presión y flujo. Se evaluó un total de 46 personas, sanos desde el punto de vista nasal, divididas en dos grupos según edad, cada uno con igual proporción de hombres y mujeres. El grupo I estuvo formado por 22 personas entre 20 y 50 años y el grupo II por 24 personas entre 51 y 80 años. Para los resultados obtenidos se calcularon medidas estadísticamente significativas al confrontar las medias de resistencia nasal total y uninasal. Al comparar por género dentro de cada grupo, sólo en el grupo I se encontró diferencias estadísticamente significativas para la varianza y el promedio

Respiratory syncytial virus-specific immunoglobulins in preterm infants.

Incomplete transfer of maternal antibodies specific to respiratory syncytial virus (RSV) has been suggested as an explanation for the increased risk of RSV infections in preterm infants. Antibodies directed against the two major RSV envelope glycoproteins, F and G, are protective in vitro and in vivo. Our study was conducted to measure IgG, IgG1, IgG2, and IgG3 antibody titers against the RSV F and G glycoproteins in cord sera from infants born at different gestational ages. Titers of neutralizing antibody were measured in a subset of the subjects. The mean (+/- SEM) log2 titers of IgG antibodies directed against the RSV F and G glycoproteins were significantly lower in infants born at < or = 28 weeks of gestation (11.2 and 10.8 for F and G glycoproteins, respectively) than in term infants (12.6 and 12.8 for F and G, respectively) (p < 0.05). Preterm infants born at > or = 29 weeks had titers of antibodies against the F glycoprotein comparable to those of term infants. The highest titers of RSV-specific antibodies were in the IgG1 and IgG2 subclasses. Mean (+/- SEM) neutralizing antibody titers were lower in infants born at < or = 28 weeks (7.7 +/- 0.4) than in term infants (10.2 +/- 0.3) (p < 0.001). We conclude that (1) RSV-specific antibody titers were lower than in term infants only in the most premature infants (< or = 28 weeks) and (2) preterm infants born at > or = 29 or > or = 33 weeks of gestation had RSV-specific titers against F and G glycoproteins, respectively, that were comparable to those of term infants. Preterm infants born at < or = 28 weeks could represent a target population for passive immunoprophylaxis.