Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity

Long-term memory is thought to be mediated by protein synthesis-dependent, late-phase long-term potentiation (L-LTP). Two secretory proteins, tissue plasminogen activator (tPA) and brain-derived neurotrophic factor (BDNF), have been implicated in this process, but their relationship is unclear. Here we report that tPA, by activating the extracellular protease plasmin, converts the precursor proBDNF to the mature BDNF (mBDNF), and that such conversion is critical for L-LTP expression in mouse hippocampus. Moreover, application of mBDNF is sufficient to rescue L-LTP when protein synthesis is inhibited, which suggests that mBDNF is a key protein synthesis product for L-LTP expression.     

Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition

Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a neuronal silencing tool, mouse RC::FPDi (based on the synthetic G protein-coupled receptor Di), designed for cell type-specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, administration of the ligand clozapine-N-oxide (CNO) by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue carbon dioxide (CO(2)) elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO(2) acidosis. Body thermoregulation at room temperature was also disrupted after CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function.     

A dog model to study ovary, ovarian ligament and visceral pain

Objective A dog model was developed to study visceral pain by stimulating the ovarian ligament. Study design Prospective experimental trial. Animals Twelve 1‐year old female hound dogs weighing 25.7 ± 3.6 kg. Methods Dogs were anesthetized with sevoflurane. The right ovary was accessed via laparoscopy. A suture was placed around the ovarian ligament and exteriorized through the abdominal wall for stimulation. The noxious stimulus consisted of pulling the ovary and ovarian ligament with a force transducer. The response to noxious stimulation was determined using the anesthetic minimum alveolar concentration requirement (MAC) for sevoflurane. The ovarian MAC was compared to the standardized somatic noxious stimulation tail clamp MAC. The results are depicted as mean ± SD and corrected to sea‐level. Results The stimulus–response curve during ovarian stimulation in three dogs was hyperbolic and best represented by a three‐parameter logistic growth curve model. The curve plateaued at 7.12 ± 4.19 N. From the stimulus‐response curve, we chose 6.61 N to test the consistency and repeatability of the model in nine dogs. The ovarian stimulation MAC for sevoflurane in these dogs was 2.16 ± 0.46%. The ovarian stimulation confidence interval and limits are comparable to the results from tail stimulation MAC. The tail stimulation MACs before and after laparoscopy surgery were not different (1.86 ± 0.28% and 1.77 ± 0.38% respectively; p > 0.05) but lower when compared to the ovarian MAC (p < 0.01). The dogs recovered from anesthesia without complications. Conclusions and clinical relevance The ovarian stimulation model is an adequate and repeatable means of producing visceral stimulation to determine MAC. The model may provide a humane mechanism to study the effectiveness of analgesics for acute ovarian pain.     

Transition From Sagebrush Steppe to Annual Grass (Bromus tectorum): Influence on Belowground Carbon and Nitrogen

Vegetation changes associated with climate shifts and anthropogenic disturbance have major impacts on biogeochemical cycling. Much of the interior western United States currently is dominated by sagebrush (Artemisia tridentata Nutt.) ecosystems. At low to intermediate elevations, sagebrush ecosystems increasingly are influenced by cheatgrass (Bromus tectorum L.) invasion. Little currently is known about the distribution of belowground organic carbon (OC) on these changing landscapes, how annual grass invasion affects OC pools, or the role that nitrogen (N) plays in carbon (C) retention. As part of a Joint Fire Sciences-funded project called the Sagebrush Treatment Evaluation Project (SageSTEP), we quantified the depth distribution of soil OC and N at seven sites experiencing cheatgrass invasion. We sampled plots that retained sagebrush, but represented a continuum of cheatgrass invasion into the understory. Eighty-four soil cores were taken using a mechanically driven diamond-tipped core drill to a depth of 90 cm, or until bedrock or a restrictive layer was encountered. Samples were taken in 15-cm increments, and soil, rocks, and roots were analyzed for OC and total N. We determined that cheatgrass influences the vertical distribution of OC and N within the soil profile and might result in decreased soil OC content below 60  cm. We also found that OC and total N associated with coarse fragments accounted for at least 10% of belowground pools. This emphasizes the need for researchers to quantify nutrients in deep soil horizons and coarse fragments.     

Endotoxin Concentrations Measured by a Chromogenic Assay in Portal and Peripheral Venous Blood in Ten Dogs With Portosystemic Shunts

A chromogenic Limulus amebocyte lysate assay was used to measure portal and peripheral venous endotoxin concentrations in ten medically managed dogs undergoing surgery for correction of a single extrahepatic portosystemic shunt. In all dogs, both peripheral and portal venous blood samples were obtained at the time of surgical manipulation of the anomalous vessel. In six dogs, peripheral venous samples were obtained an average of 8.0 months after surgery. Five physically normal dogs without biochemical or histologic evidence of liver disease served as controls. Data analysis failed to demonstrate significant differences in peripheral and portal venous endotoxin concentrations between the control and study groups. Postoperatively five of six dogs showed a measurable reduction in peripheral venous endotoxin concentration over intraoperatively obtained values, but the differences were not statistically significant (P = 0.06). Based on results of this study it was concluded that systemic endotoxemia was not present in dogs with a single extrahepatic portosystemic shunt that were medically stable prior to surgery.     

USE OF QUANTITATIVE HEPATIC SCINTIGRAPHY TO EVALUATE SPONTANEOUS PORTOSYSTEMIC SHUNTS IN 12 DOGS

Quantitative hepatic scintigraphy is a valid means for estimating total liver blood flow and relative portal hepatic perfusion. The Hepatic perfusion index (HPI) was determined for a group of 12 dogs with portosystemic shunts prior to and two days after corrective surgery. HPI values for the dogs prior to operation were significantly elevated (p<0.001) as compared with those for a group of normal dogs, indicating reduced effective portal hepatic perfusion in dogs with shunts. Dogs showing a favorable clinical response after surgery had a significant decrease (p<0.02) in HPI values after operation. One dog showing a poor clinical response after operation had an increase in HPI score after operation. Quantitative hepatic scintigraphy is a valuable diagnostic test for screening presumptive cases of portosystemic shunts and monitoring the response to surgical intervention.     

A longitudinal study of sows and boars raised by smallholder farmers in the Philippines

We conducted a longitudinal study to obtain baseline information about the health and productivity of sows and boars raised by smallholder-pig raisers in the Philippines, and test constraints and opportunities to smallholder-sow production that had been identified previously in a cross-sectional study [More, S.J., Lee, J.-A.L.M., La?ada, E.B., Taveros, A.A., Cotiw-an, B.S., 1999. Weight-for-age of growing pigs raised by smallholder farmers in the Philippines. Prev. Vet. Med. 41, 151-169]. Over 12-18 months, we collected data during monthly on-farm visits about 213 sows raised in 119 herds at 2 sites and 32 boars in 31 herds at 1 site. Sow reproductive performance was low and boars were used only infrequently (an average of 0.9 services/month). Using repeated-measure analyses, we identified sow nutrition and piglet care (such as provision of creep feed and unrestricted access to the sow) as important husbandry issues associated with increased sow productivity.     

A longitudinal study of unweaned piglets raised by smallholder farmers in the Philippines

We conducted a longitudinal study to obtain detailed baseline information about the health and productivity of unweaned piglets raised by smallholder pig raisers in the Philippines, and to identify constraints and opportunities to smallholder-piglet production. At two sites in the Philippines, we collected data about 242 litters from 173 sows in 102 herds during on-farm visits over 12-18 months. Preweaning mortality at the northern and southern sites was 17 and 9%, respectively. Of the piglet deaths at the northern site, 49% occurred within 24h of birth. Pig raisers used few of the recognised interventions known to reduce neonatal piglet mortality, although >50% of litters were given iron injections at the northern site and kept in a farrowing pen with a barrier at the southern site. Creep feeding was more common at the northern site but the nutritive value of the feeds given to piglets was low. We used repeated-measures and time-to-event analyses. Our results suggest that targeted extension (addressing, in particular, management issues relating to neonatal piglets) can contribute to increased productivity of unweaned piglets.     

Evaluation of xylazine and ketamine for total intravenous anesthesia in horses

OBJECTIVE: To evaluate the use of xylazine and ketamine for total i.v. anesthesia in horses. ANIMALS: 8 horses. PROCEDURE: Anesthetic induction was performed on 4 occasions in each horse with xylazine (0.75 mg/kg, i.v.), guaifenesin (75 mg/kg, i.v.), and ketamine (2 mg/kg, i.v.). Intravenous infusions of xylazine and ketamine were then started by use of 1 of 6 treatments as follows for which 35, 90, 120, and 150 represent infusion dosages (microg/kg/min) and X and K represent xylazine and ketamine, respectively: X35 + K90 with 100% inspired oxygen (O2), X35 + K120-(O2), X35 + K150-(O2), X70 + K90-(O2), K150-(O2), and X35 + K120 with a 21% fraction of inspired oxygen (ie, air). Cardiopulmonary measurements were performed. Response to a noxious electrical stimulus was observed at 20, 40, and 60 minutes after induction. Times to achieve sternal recumbency and standing were recorded. Quality of sedation, induction, and recovery to sternal recumbency and standing were subjectively evaluated. RESULTS: Heart rate and cardiac index were higher and total peripheral resistance lower in K150-(O2) and X35 + K120-air groups. The mean arterial pressure was highest in the X35 + K120-air group and lowest in the K150-(O2) group (125 +/- 6 vs 85 +/- 8 at 20 minutes, respectively). Mean Pa(O2) was lowest in the X35 + K120-air group. Times to sternal recumbency and standing were shortest for horses receiving K150-(O2) (23 +/- 6 minutes and 33 +/- 8 minutes, respectively) and longest for those receiving X70 + K90-(O2) (58 +/- 28 minutes and 69 +/- 27 minutes, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Infusions of xylazine and ketamine may be used with oxygen supplementation to maintain 60 minutes of anesthesia in healthy adult horses.     

Intracranial elastance in isoflurane-anesthetized horses

OBJECTIVE: To determine whether high intracranial pressure (ICP) during spontaneous ventilation (SV) in anesthetized horses coincides with an increase in intracranial elastance (ie, change in ICP per unit change of intracranial volume). ANIMALS: 6 adult horses. PROCEDURE: Anesthesia was induced and maintained in each horse for 5 hours with isoflurane at a constant dose equal to 1.2 times the minimum alveolar concentration. Direct ICP measurements were obtained by use of a strain gauge transducer inserted in the subarachnoid space, and arterial blood pressure was measured from a carotid artery. Physiologic responses were recorded after 15 minutes of normocapnic controlled ventilation (CV) and then after 10 minutes of SV. Aliquots (3 mL) of CSF were removed from each horse during SV until ICP returned to CV values. Slopes of pressure-volume curves yielded intracranial elastance. RESULTS: Intracranial elastance ranged from 0.2 to 3.7 mm Hg/mL after removal of the first aliquot of CSF Slopes of pressure-volume curves were largest following removal of the initial CSF aliquot, but shallow portions of curves were detected at relatively high ICPs (25 to 35 mm Hg). A second-order relationship between SV ICP and initial intracranial elastance was found. CONCLUSIONS AND CLINICAL RELEVANCE: In horses anesthetized with isoflurane, small changes in intracranial volume can cause large changes in ICP Increased intracranial elastance could further exacerbate preexisting intracranial hypertension. However, removal of small volumes of CSF may cause rapid compensatory replacement from other intracranial compartments, which suggests steady-state maintenance of an increase in intracranial volume during isoflurane anesthesia in horses.