Congenital intestinal stenosis and Hirschsprung's disease: two extremely rare pathologies in a newborn puppy.

BACKGROUND: Hirschsprung's disease (HSCR) is a common congenital malformation of the enteric nervous system (ENS). During fetal development, ganglion cells of the ENS are derived from neural crest cells that migrate to the bowel. These cells reside principally in two ganglionated plexus: 1) The myenteric plexus, extending from the esophagus to the anus, and 2) submucous plexus, extending from the duodenum to the anus. In large animal species, there is a third plexus called Henle's or Schabadasch's plexus. ENS ganglion cells play a key role in normal gastrointestinal motility, respond to sensory stimuli and regulate blood flow. Both plexus show a high degree of independence from the central nervous system. Alterations in the embryonic development of the ENS can induce multiple pathologies in animal models and humans. CASE PRESENTATION: The present case was a female the fifth born in a litter of 5 puppies. At about 2-3 weeks of age, she suffered from abdominal distension, pain, and constipation. At approximately 8-10 weeks of age, the puppy started to vomit abundantly, and the regurgitated food appeared undigested. Progressive abdominal distention was observed, with quite visible peristaltic movements and more frequent vomiting episodes. The abdominal radiographs, based on AP and side projections, revealed an enlargement of the abdominal diameter and an increased width in the epigastric region. At 12 weeks of age, exploratory surgery revealed a stenotic segment in the jejunum, followed by a small transition zone and then a significantly reduced diameter. Immunohistochemical examinations were performed using antibodies against calretinin, S-100 protein, CD56, neuron specific enolase (NSE) and synaptophysin, which are the biological markers for diagnosing HSCR. CONCLUSION: A reduced number of ganglion cells (1-3 cells per ganglion) were found. There was no specific staining pattern for many of these; while for others, the pattern was compatible with HSCR. Surgical intervention to remove the stenotic section prolonged the life of the puppy for 13 years. Extremely rare pathologies such as that discussed herein should be studied to understand the pathophysiology and be able to diagnose small species in veterinary medicine in a timely fashion. To our knowledge, this is the first report of congenital intestinal stenosis and Hirschprung's disease in a newborn puppy.

Appendiceal carcinoma associated with microsatellite instability.

Approximately 15% of colorectal cancer (CRC) cases exhibit microsatellite instability (MSI), which appears to be associated with unique biological behavior. The present study presents a case of appendiceal carcinoma associated with MSI that responded well to adjuvant chemotherapy. Clinical, pathological and immunohistochemical (IHC) characteristics have been described. The 60-year-old male patient had suffered from recurrent lower abdominal pain associated with abdominal distention for 6 months; then, following an acute attack, he was subjected to laparoscopic appendectomy. The histopathological examination revealed moderately differentiated appendiceal adenocarcinoma with mucinous areas, without lymphovascular or perineural invasion. The IHC examination was positive for keratin-20 and caudal type homeobox 2, and negative for MutL Homolog 1, MutS Homolog (MSH) 2 and MSH-6. A postoperative colonoscopy revealed diverticulosis, without the presence of polyps or tumors. However, an abdominal axial computerized tomography scan revealed thickening of the distal portion of the appendix, increased density of the greater omentum, and metastases to the liver capsule, spleen and peritoneum. The treatment of choice was right hemicolectomy with peritoneal debulking, followed by 10 cycles of chemotherapy with 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX regimen). After 5 years of follow-up, the patient remains in good condition, without clinical or radiological signs of recurrence. The good response to chemotherapy corresponds with the observations made in other colon cancers with MSI. Therefore, testing for MSI in appendiceal carcinomas may provide useful information on prognosis and predict response to chemotherapy.

Orcinol derivative compound with antioxidant properties protects Langerhans islets against streptozotocin damage.

OBJECTIVE: To design and synthesize an orcinol derivative compound, 3-formyl-2,4-dihydroxy-5,6-dimethyl sodium benzoate (A4), as an antioxidant molecule and to test its effects on oxidative stress in an in-vitro model of apoptosis of pancreatic rat beta cells induced by streptozotocin (STZ). METHODS: Scavenger properties of A4 were assessed using its capacity to capture the DPPH radical in vitro. Antiapoptotic properties of A4 were analysed by electron microscopy and TUNEL assay in rat pancreatic islets in a streptozotocin model. KEY FINDINGS: The results show that A4 displays antioxidant activity in in-vitro assays and induced a significant reduction in STZ-induced beta cell apoptosis and low ultrastructural damage to cellular organelles in the rat pancreatic islets as evidenced by electronic microscopy, this effect could be attributed to its antioxidant activity in a similar manner than resveratrol. CONCLUSION: The overall results indicate that the new orcinol derivative molecule displays both antioxidant and antiapoptotic effects and protect pancreatic beta cells against STZ damage.

Individual differences in testosterone and corticosterone levels in relation to early postnatal development in the rabbit Oryctolagus cuniculus.

Many aspects of an animal's early development contribute to the emergence of individual differences in physiology. Here we asked whether litter size, birth mass, suckling success and postnatal growth were predictors of individual differences in testosterone (T) and corticosterone (CORT) levels in neonatal domestic rabbits. Serum concentrations of both hormones, which we measured on postnatal day 8, were significantly and positively correlated with pup growth and milk intake. Litter size and birth mass were not significantly correlated with levels of T and CORT, although both parameters were indirectly associated with the levels of these hormones via their effects on milk intake and pup growth. Our results highlight the importance of naturally occurring features of the postnatal environment in shaping individual differences in T and CORT levels during early life.

[Steroid hormones and pancreas: a new paradigm]. / Las hormonas esteroides y el páncreas: un nuevo paradigma.

The relation between steroid hormones and pancreatic function has been poorly discussed and not very well understood. In general, there is a lack of recognition among the scientific community about the importance of steroids in pancreatic function (current paradigm). In the present article we present basic, as well as clinic and epidemiologic data that demonstrate steroid synthesis and steroid biotransformation by pancreatic tissue, how exocrine and endocrine functions are modulated by steroids, the gender specific frequency and behavior of some tumors and the use of synthetic steroids and steroid action antagonists as therapeutic agents. With the available information it is possible to establish that: 1. Pancreatic tissue synthesize and transform steroid hormones. 2. Pancreatic tissue respond to steroid hormones and express steroid specific receptor molecules. 3. Some endocrine functions such as insulin synthesis and release are modulated by steroids. 4. Tumor growth is modulated by steroids and anti-steroid drugs. This set of data creates a new paradigm for the holistic study of pancreas and opens new research fields. The application of this new paradigm might result in an increase in the knowledge of pancreatic physiology, in the design of new and better diagnostic methods and eventually in the design of more effective medical treatments for the pancreatic cancers.

Las hormonas esteroides y el páncreas: Un nuevo paradigma / Steroid hormones and pancreas: A new paradigm

The relation between steroid hormones and pancreatic function has been poorly discussed and not very well understood. In general, there is a lack of recognition among the scientific community about the importance of steroids in pancreatic function (current paradigm). In the present article we present basic, as well as clinic and epidemiologic data that demonstrate steroid synthesis and steroid biotransformation by pancreatic tissue, how exocrine and endocrine functions are modulated by steroids, the gender specific frequency and behavior of some tumors and the use of synthetic steroids and steroid action antagonists as therapeutic agents. With the available information it is possible to establish that: 1. Pancreatic tissue synthesize and transform steroid hormones. 2. Pancreatic tissue respond to steroid hormones and express steroid specific receptor molecules. 3. Some endocrine functions such as insulin synthesis and release are modulated by steroids. 4. Tumor growth is modulated by steroids and anti-steroid drugs. This set of data creates a new paradigm for the holistic study of pancreas and opens new research fields. The application of this new paradigm might result in an increase in the knowledge of pancreatic physiology, in the design of new and better diagnostic methods and eventually in the design of more effective medical treatments for the pancreatic cancers.

La relación de las hormonas esteroides con el páncreas ha sido muy poco explorada y comprendida y no se concede en general que exista una interacción relevante entre su función y los esteroides endógenos o exógenos (paradigma actual). En esta revisión se presentan datos de modelos experimentales y de estudios clínicos y epidemiológicos que demuestran que existe una clara relación entre la biotransformación y el efecto de las hormonas esteroides y la fisiopatología del páncreas. Con la información disponible se puede establecer que: 1. El páncreas es un órgano que sintetiza y transforma hormonas esteroides. 2. Que expresa receptores específicos para este tipo de substancias. 3. Que algunas de sus funciones como la síntesis y liberación de la insulina pueden ser modulados por la acción de esteroides gonadales. 4. Que el crecimiento tumoral puede ser inducido o frenado por la acción de esteroides y antiesteroides. Estas relaciones establecen un nuevo paradigma en el estudio de la fisiopatología del páncreas y abren nuevas líneas de investigación para el avance del conocimiento y su eventual aplicación clínica.