Impact of a multicarbohydrase containing α-galactosidase and xylanase on ileal digestible energy, crude protein digestibility, and ileal amino acid digestibility in broiler chickens.

Exogenous enzymatic supplementation of poultry feeds, including α-galactosidase and xylanase, has been shown to increase metabolically available energy, although little information has been published on the impact on amino acid digestibility. An experiment was conducted to investigate a multicarbohydrase containing α-galactosidase and xylanase on amino acid digestibility, ileal digestible energy (IDE), and CP in male broiler chicks. The experiment was a 2 × 2 (diet × enzyme) factorial arrangement with 15 replicates of 8 male broilers per replicate raised for 21 d in a battery setting. The 2 dietary treatments included a positive control (PC) and a negative control (NC) diet formulated to contain 2.5% less calculated AME and digestible amino acids. Each of these diets was fed with and without enzyme. Broilers were fed a starter diet from 0-14 d (crumble) and a grower from 14-21 d (pellet). Birds were sampled on day 21 to determine ileal amino acid digestibility, IDE, and CP digestibility. Titanium dioxide (TiO2) was used as an indigestible marker for the determination of digestibility coefficients. Total ileal amino acid digestibility was increased (P = 0.008) by 3.80% with the inclusion of enzyme. Methionine and lysine digestibility was improved (P < 0.05) with the inclusion of enzyme by 3.37% and 2.61%, respectively. Enzyme inclusion increased (P = 0.001) cysteine digestibility by 9.3%. Diet-influenced ileal amino acid digestibility with tryptophan, threonine, isoleucine, and valine digestibility being increased (P < 0.05) in the PC when compared to the NC. IDE was decreased (P = 0.037) in broilers fed the NC diet by 100 kcal/kg feed when compared to broilers fed the PC diet. Enzyme inclusion increased (P = 0.047) IDE value by 90 kcal/kg. Crude protein digestibility was not influenced by diet; however, similar improvements in CP digestibility with enzyme inclusion were observed as with energy. These data support the benefits of a multicarbohydrase containing α-galactosidase and xylanase inclusion to improve nutrient and ileal amino acid digestibility across multiple dietary nutrient profiles.

Efficacy of ß-mannanase on broiler growth performance and energy utilization in the presence of increasing dietary galactomannan.

An experiment was conducted to investigate the impact of ß-mannanase inclusion on growth performance, viscosity, and energy utilization in broilers fed diets varying in galactomannan (GM) concentrations. Treatments were arranged as a 3 (GM concentration) × 3 (ß-mannanase inclusion) factorial randomized complete block design with 12 replicates of 29 male broilers per replicate for a 42-d experiment. Efforts were made to reduce the amount of soybean meal, and thus GM, in the basal diet with guar gum included at 0, 0.21, or 0.42% to achieve a GM supplementation of 1,500 and 3,000 ppm, respectively. Beta-mannanase was included at 0, 200, or 400 g/ton. Broilers were fed a starter (d 0 to 14), grower (d 15 to 28), and finisher diets (d 29 to 42). Growth performance was monitored and ileal contents collected on d 14, 28, and 42 to determine ileal digestible energy (IDE) and intestinal viscosity. Increasing levels of GM negatively (P < 0.05) influenced body weight (BW) following the starter and grower periods and increased (P < 0.01) mortality corrected feed conversion ratio (FCR) throughout the study. Reduced growth performance was associated with increased (P < 0.05) intestinal viscosity and decreased (P < 0.05) IDE when GM inclusion was increased. Inclusion of ß-mannanase in diets containing supplemental GM on d 28, increased average BW to levels similar to diets without supplemental GM. Improvements in FCR were also observed with ß-mannanase inclusion in diets containing supplemental GM. Ileal digestible energy was increased (P < 0.05) with the addition of ß-mannanase on d 28 of age. Multiple interactions in growth performance, intestinal viscosity, and IDE were associated with ß-mannanase administration. In conclusion, ß-mannanase improved IDE, reduced intestinal viscosity, and improved growth performance; however, the observed benefit was dependent upon dietary GM concentration.

Changes in immune and metabolic gut response in broilers fed ß-mannanase in ß-mannan-containing diets.

ß-galactomannans found in soy-based broiler feed are known to cause physiological effects that are hypothesized to be related to gut inflammation. Previous studies have shown that the incorporation of ß-mannanase in the diet or as a supplement results in improvements to certain performance parameters related to gut health and feed conversion. Using kinome analysis, we characterized the mechanism of ß-galactomannan activity and supplementation with ß-mannanase on the gut of commercial broilers to understand the mode of action. Two doses of ß-mannanase (200 and 400 g/ton of feed) with and without inclusion of additional ß-galactomannan (3,000 ppm) were tested at 3 time points (d 14, d 28, and d 42 post hatch). Broilers were fed starter (d 0 to 14), grower (d 15 to 28), and finisher diets (d 29 to 42). Jejuna were collected from birds from each treatment condition and time point. Cluster analysis of the kinome data showed that birds clustered first by age, then predominantly by whether ß-mannanase had been included in the diet. Biological pathway analysis showed that the inclusion of additional ß-galactomannan into the diet resulted in increased signaling related to immune response, relative to our normal control diet (with reduced soybean meal). The addition of ß-mannanase to the enhanced ß-galactomannan diet eliminated the majority of this immune-related signaling, indicating that the feed-induced immune response within the jejuna had been eliminated by the addition of ß-mannanase. We also saw changes in specific metabolic and gut function pathways in birds fed ß-mannanase. These observed changes in ß-mannanase-fed birds are likely the mechanism for the enhanced performance and feed conversion observed in birds given ß-mannanase in their diets.

Molecular analysis of changes in Pseudomonas aeruginosa load during treatment of a pulmonary exacerbation in cystic fibrosis.

BACKGROUND: Intravenous antibiotics for pulmonary exacerbations (PEs) of cystic fibrosis (CF) usually target Pseudomonas aeruginosa. Insights into the CF lung microbiome have questioned this approach. We used RT-qPCR to determine whether intravenous antibiotics reduced P. aeruginosa numbers and whether this correlated with improved lung function. We also investigated antibiotic effects on other common respiratory pathogens in CF. METHODS: Sputa were collected from patients when stable and again during a PE. Sputa were expectorated into a RNA preservation buffer for RNA extraction and preparation of cDNA. qPCR was used to enumerate viable P. aeruginosa as well as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Burkholderia cepacia complex and Aspergillus fumigatus. RESULTS: Fifteen CF patients were followed through 21 PEs. A complete set of serial sputum samples was unavailable for two patients (three separate PEs). P. aeruginosa numbers did not increase immediately prior to a PE, but numbers during intravenous antibiotic treatment were reduced ≥4-log in 6/18 and ≥1-log in 4/18 PEs. In 7/18 PEs, P. aeruginosa numbers changed very little with intravenous antibiotics and one patient demonstrated a ≥2-log increase in P. aeruginosa load. H. influenzae and S. pneumoniae were detected in ten and five PEs respectively, but with antibiotic treatment these bacteria rapidly became undetectable in 6/10 and 4/5 PEs, respectively. There was a negative correlation between P. aeruginosa numbers and FEV1 during stable phase (r(s)=0.75, p<0.05), and reductions in P. aeruginosa load with intravenous antibiotic treatment correlated with improved FEV1 (r(s)=0.52, p<0.05). CONCLUSIONS: Exacerbations are not due to increased P. aeruginosa numbers in CF adults. However, lung function improvements correlate with reduced P. aeruginosa burden suggesting that current antibiotic treatment strategies remain appropriate in most patients. Improved understanding of PE characterised by unchanged P. aeruginosa numbers and minimal lung function improvement following treatment may allow better targeted therapies.

Altered connections on the road to psychopathy.

Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, however, has ever studied the white matter connections (such as the uncinate fasciculus (UF)) linking these structures in psychopaths. Therefore, we used in vivo diffusion tensor magnetic resonance imaging (DT-MRI) tractography to analyse the microstructural integrity of the UF in psychopaths (defined by a Psychopathy Checklist Revised (PCL-R) score of > or = 25) with convictions that included attempted murder, manslaughter, multiple rape with strangulation and false imprisonment. We report significantly reduced fractional anisotropy (FA) (P<0.003), an indirect measure of microstructural integrity, in the UF of psychopaths compared with age- and IQ-matched controls. We also found, within psychopaths, a correlation between measures of antisocial behaviour and anatomical differences in the UF. To confirm that these findings were specific to the limbic amygdala-OFC network, we also studied two 'non-limbic' control tracts connecting the posterior visual and auditory areas to the amygdala and the OFC, and found no significant between-group differences. Lastly, to determine that our findings in UF could not be totally explained by non-specific confounds, we carried out a post hoc comparison with a psychiatric control group with a past history of drug abuse and institutionalization. Our findings remained significant. Taken together, these results suggest that abnormalities in a specific amygdala-OFC limbic network underpin the neurobiological basis of psychopathy.

A TSM sensor investigation of low crystallinity cellulose films.

A thickness shear mode (TSM) quartz sensor has been used to characterize the substantivity, viscoelasticity, and mucoadhesive properties of low crystallinity cellulose (LCC) films. LCC is a novel pharmaceutical excipient that has been attributed with mucoadhesive properties. Thin films of LCC were deposited onto TSM sensors by a spin coating technique. The films were treated by passing water or 1.0% w/v mucin solution (pH 3.7 or 7.0) over the surface. Changes in the mass and viscosity of the film were observed by monitoring changes in the impedance spectra of the coated TSM sensors. Scanning electron micrographs (SEMs) of each film were used to assist the interpretation of the TSM sensor data. This study showed that LCC forms highly tenacious and viscoelastic films able to withstand prolonged (approximately 1 h) exposure to both water and mucin solution. Furthermore, these results indicate that the films may have mucoadhesive properties as LCC was found to bind significant (P<0.05) amounts of mucin in comparison with control measurements. Mucin binding to the LCC sensor was greater at pH 3.7 (P<0.05) than at pH 7.0, suggesting that the LCC formulation is mucoadhesive under these conditions.

The role of arterial elastance in ventricular-arterial coupling in normal gravity and altered acceleration environments.

The role of physiological elastance (Ep) in maximizing external work (EW) transfer is not well understood and has not been investigated during microgravity and increased acceleration conditions. By better understanding this relationship, cardiovascular control mechanisms for meeting metabolic demands during normal gravity and altered acceleration stresses may be elucidated. Therefore, the objectives of this study were to determine the effect of Ep in maximizing EW of the left ventricle and to investigate this relationship during altered acceleration states. Ventricular and arterial parameters were estimated using established lumped parameter models from isolated beats of experimental data. These data were obtained during parabolic flight (0 and approximately 2 Gz) and centrifuge runs (approximately 1 to approximately 4 Gz) where acceleration was used to drive the cardiovascular system into a wide range of physiologic operating and coupling conditions. Parameter estimates at each Gz level were used in a series of computer simulations in which Ep was varied over a wide range to find the point of maximum EW for that coupling condition. Cardiac output and mean arterial pressure were maintained throughout the simulation process by adjusting heart rate. Results of the simulation showed that as arterial elastance decreased from its initially estimated (physiologic) value, external work increased slightly and as elastance increased, external work decreased. In particular, we found that the arterial elastance was set at a point near that which would produce maximal external work. In addition, it was found that altered Gz states may affect the Ep-EW relationship.

The association of diabetes and glucose control with surgical-site infections among cardiothoracic surgery patients.

OBJECTIVE: To assess the importance of diabetes, diabetes control, hyperglycemia, and previously undiagnosed diabetes in the development of surgical-site infections (SSIs) among cardiothoracic surgery patients. SETTING: A 540-bed tertiary-care university-affiliated hospital. DESIGN: Prospective cohort and case-control studies. PATIENTS: All patients having cardiothoracic surgery between November 1998 and September 1999 were eligible for participation. One thousand patients had preoperative hemoglobin A1c determinations. Seventy-four patients with SSIs were identified. RESULTS: Diabetes (odd ratio [OR], 2.76; P<.001) and postoperative hyperglycemia (OR, 2.02; P=.007) were independently associated with development of SSIs. Among known diabetics, elevated hemoglobin A1c values were not associated with a statistically significantly increased risk of infection; the mean A1c value was 8.44% among those with infections compared with 7.80% for those without (P=.09). Forty-two (6%) of 700 patients without prior diabetes history had evidence of undiagnosed diabetes; their infection rate was comparable to that of known diabetics (3/42 [7%] vs 17/300 [6%]; P=.72). An additional 30% of nondiabetics had elevated hemoglobin A1c determinations or perioperative hyperglycemia. CONCLUSIONS: Postoperative hyperglycemia and previously undiagnosed diabetes are associated with development of SSIs among cardiothoracic surgery patients. Screening for diabetes and hyperglycemia among patients having cardiothoracic surgery may be warranted to prevent postoperative and chronic complications of this metabolic abnormality.

In vitro iontophoretic release of lithium chloride and lidocaine hydrochloride from polymer electrolytes.

Ionically conducting polymers, frequently known as polymer electrolytes, are potential candidates as hosts for drugs to be delivered iontophoretically. The iontophoretic delivery of lithium or lidocaine from polymer electrolyte films through a cellophane membrane was examined using different delivery current regimes. Thin, mechanically strong, polymer electrolyte films were fabricated from poly(ethylene oxide) (PEO) with lithium chloride or lidocaine hydrochloride. Experiments showed that iontophoretic transport of both lithium chloride and lidocaine hydrochloride might be achieved from these PEO-based films. Cation transport number determinations give values for PEO-based films of about 0.4 for lithium chloride systems and 0.12 for lidocaine hydrochloride systems. The mechanism of transport from these PEO-based polymer electrolyte films allows the delivery of ionic salts such as lithium chloride and lidocaine hydrochloride to be controlled solely by current, thus providing a system that can deliver precise amounts of drug.

Bipolaris spicifera meningitis complicating a neurosurgerical procedure.

Bipolaris spicifera, one of the darkly pigmented (dematiaceous) fungi commonly found in soil, is an uncommon cause of infection in humans and an unusual cause of meningitis and nosocomial infections. An 18-y-old boy who experienced meningitis with this micro-organism after acoustic neuroma resection was successfully treated with amphotericin B.

Characterisation of fatty acid multilayers using a TSM biosensor.

Thickness shear mode (TSM) biosensors have many potential applications within the pharmaceutical sciences as a means of measuring mass changes in the nanogram range, film thickness, viscosity and shear moduli. This study addresses the possible use of the TSM sensor as a biosensor for measuring drug partition coefficients. In order to realise this potential, some fundamental understanding is required of the behaviour of lipid films on the sensor. The present study characterises the behaviour of fatty acid multilayers as a suitable model chemical system. Frequency shifts and impedance spectra are presented for multilayers of three fatty acid films coated on to the sensor using a Langmuir-Blodgett trough. The results indicate that the frequency shift is non-linear at lower numbers of fatty acid layers but the response is Sauerbrey-like at higher numbers of layers. Also at high numbers of layers, changes in the impedance spectra indicate viscoelastic behaviour in thicker membranes. An inverse relationship is observed between chain length and frequency shift, which is attributed to variations in the topography of the sensor surface. This work demonstrates the importance of fully characterising the physical behaviour of the lipid multilayers prior to using these systems for the measurement of drug partition coefficients.

Fast estimation of arterial vascular parameters for transient and steady beats with application to hemodynamic state under variant gravitational conditions.

Numerous parameter estimation techniques exist for characterizing the arterial system using electrical circuit analogs. These techniques are often limited by requiring steady-state beat conditions and can be computationally expensive. Therefore, a new method was developed to estimate arterial parameters during steady and transient beat conditions. A four-element electrical analog circuit was used to model the arterial system. The input impedance equations for this model were derived and reduced to their real and imaginary components. Next, the physiological input impedance was calculated by computing fast Fourier transforms of physiological aortic pressure (AoP) and aortic flow. The approach was to reduce the error between the calculated model impedance and the physiological arterial impedance using a Jacobian matrix technique which iteratively adjusted arterial parameter values. This technique also included algorithms for estimating physiological arterial parameters for nonsteady physiological AoP beats. The method was insensitive to initial parameter estimates and to small errors in the physiological impedance coefficients. When the estimation technique was applied to in vivo data containing steady and transient beats it reliably estimated Windkessel arterial parameters under a wide range of physiological conditions. Further, this method appears to be more computationally efficient compared to time-domain approaches.

Cleft lip and palate treated by presurgical orthopedics, gingivoperiosteoplasty, and lip adhesion (POPLA) compared with previous lip adhesion method: a preliminary study of serial dental casts.

Comparing the treatment protocols for cleft lip and palate requires a study of facial growth and development. Serial orthodontic study models aid in delineating the effects of surgery on maxillary mandibular relationships. In 1978, a new protocol, POPLA (presurgical orthopedics followed by periosteoplasty and lip adhesion), was developed and put into practice. This article compares the results obtained using POPLA (group I) with those using the previous method (lip adhesion alone) (group II) for cases of unilateral and bilateral clefts. Complete orthodontic study models were available for 124 patients, 63 in group I and 61 in group II. Specific timing sequences and surgical details are discussed. Dental cast analyses evaluated alveolar gap, arch width, anteroposterior distance, incisor crossbite (single tooth and multiple tooth), and buccal crossbite (single and multiple tooth) at birth and at 3, 6, and 9 years of age. X-ray studies evaluated the bony bridge. Additional comments are made regarding the incidents and effects of pharyngeal flaps and bone grafts on maxillary-mandibular relationships. Results included less buccal crossbite in the POPLA group, with a wider transverse distance of the upper dental arch. There was a greater frequency of anterior crossbite in the POPLA group, and the anteroposterior distance was shorter at 6 years of age but less so by age 9. This may be because of the different orthodontic care received by the patients in the two groups. In conclusion, the POPLA approach achieves the main goal of moving the palate into a normal position and stabilizing the arch with a bony bridge that attracts teeth. It avoids the difficult anterior fistulae and presents a more symmetrical platform upon which the lip can be united and the nose can be corrected early.

Physical characterization of polymer electrolytes as novel iontophoretic drug delivery devices.

Polymer electrolytes are solid-like materials formed by dispersing a salt at the molecular level in a high molecular weight polymer such as poly(ethylene oxide) (PEO). They have been extensively studied for use in electrochemical applications such as batteries and display devices. This paper considers a novel application of polymer electrolytes as the basis of iontophoretic drug delivery systems. Polymer electrolyte films were cast from solutions of PEO and various drug salts using either water or an acetonitrile/ethanol mixture as the solvent. These films were characterized by variable-temperature polarizing microscopy (VTPM), differential scanning calorimetry (DSC), and alternating current (AC) impedance analysis. The films were around 100-micron thick and mechanically strong; the optical and thermal methods provided evidence that the polymer electrolytes had crystalline and amorphous phases, although some drugs may exist in films as nanodispersions. The amorphous phase is important as ions have greater mobility in this phase and therefore allow a current to be passed when the material is incorporated into a device such as one suitable for drug delivery by iontophoresis. The AC impedance analysis showed that the conductivity of the films varied between 10(-6) and 10(-3) S cm-1, depending on the salt, casting solvent, and temperature. Two drugs in particular were shown to be promising candidates in these systems: lidocaine hydrochloride and lithium chloride.

Evaluation of dual-tip micromanometers during 21-day implantation in goats.

Investigative research efforts using a cardiovascular model required the determination of central circulatory haemodynamic and arterial system parameters for the evaluation of cardiovascular performance. These calculations required continuous beat-to-beat measurement of pressure within the four chambers of the heart and great vessels. Sensitivity and offset drift, longevity, and sources of error for eight 3F dual-tipped micromanometers were determined during 21 days of implantation in goats. Subjects were instrumented with pairs of chronically implanted fluid-filled access catheters in the left and right ventricles, through which dual-tipped (test) micromanometers were chronically inserted and single-tip (standard) micromanometers were acutely inserted. Acutely inserted sensors were calibrated daily and measured pressures were compared in vivo to the chronically inserted sensors. Comparison of the pre- and post-gain calibration of the chronically inserted sensors showed a mean sensitivity drift of 1.0 +/- 0.4% (99% confidence, n = 9 sensors) and mean offset drift of 5.0 +/- 1.5 mmHg (99% confidence, n = 9 sensors). Potential sources of error for these drifts were identified, and included measurement system inaccuracies, temperature drift, hydrostatic column gradients, and dynamic pressure changes. Based upon these findings, we determined that these micromanometers may be chronically inserted in high-pressure chambers for up to 17 days with an acceptable error, but should be limited to acute (hours) insertions in low-pressure applications.

Evidence for increased cardiac compliance during exposure to simulated microgravity.

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

Tubule density of the stratum medium of horse hoof.

The number of tubules/mm2 (tubule density) of horse hoof horn was quantified in samples taken from the left forefeet of 8 randomly selected slaughterhouse horses in order to establish the normal tubule density characteristics at the midline dead centre (MDC) for the stratum medium of horse hoof. In the past the measurement of tubule distribution within the hoof has lacked objectivity. The horse hoof tubule density results are compared to a recent objective study carried out on pony hoof. A similar 4 zone pattern of tubule density was observed, although the precise zonal boundaries and tubule density values differed to those found for pony hoof. There were significant differences in tubule density between zones. Comparison with pony hoof revealed significant tubule density differences in zones 1, 2 and 4; however, there was no significant difference in zone 3. The existence of a 4 zoned pattern of tubule density for horse hoof, as for pony hoof, has been confirmed.

Finite element analysis of static loading in donkey hoof wall.

A finite element model of donkey hoof wall was constructed from measurements taken directly from the hoof capsule of the left forefoot. The model was created with a 2 mm mesh and consisted of 11,608 nodes. A linear elastic analysis was conducted assuming isotropic material properties in response to a 375 newton (N) load, to simulate static loading. The load was applied to the wall via 400 laminae in order to simulate the way in which the pedal bone is suspended within the donkey hoof capsule. Displacement, stress concentration, principal strain, and force distribution across the hoof wall were evaluated. The hoof wall model revealed loading responses that were in broad agreement with previously reported in vivo and modelled observations of the equid hoof. Finite element analysis offers the potential to model hoof wall function at the macroscopic and microscopic level. In this way, it could help to develop further our understanding of the functional relationship between the structural organisation and material properties of the hoof wall.