Factors affecting ciliary beat frequency in the intrapulmonary airways of rats.

The influence of drugs on ciliary beat frequency in the intrapulmonary airways of rats was studied in vitro. Sympathomimetic drugs significantly increased the ciliary beat frequency. Acetylcholine, pilocarpine, aminophylline, prednisolone, potassium iodide, and ammonium chloride also caused cilioexcitation, though to a lesser degree. Phentolamine, 5-hydroxytryptamine, histamine, and acetylcysteine caused an apparent cilioinhibition. However, histamine in high doses also caused an incoordination of ciliary beat. Codeine and phenobarbital were slightly cilioexcitatory in low concentrations and ciliodepressive at higher concentrations.     

A viscoelastic two-dimensional network model of the lung extracellular matrix

Biomechanics and Modeling in Mechanobiology - The extracellular matrix (ECM) comprises a large proportion of the lung parenchymal tissue and is an important contributor to the mechanical properties...     

Viscerotropic growth pattern of Leishmania tropica in BALB/c mice is suggestive of a murine model for human viscerotropic leishmaniasis

Leishmania (L.) tropica is a causative agent of cutaneous leishmaniasis, and occasionally of visceral or viscerotropic leishmaniasis in humans. Murine models of Leishmania infection have been proven to be useful for elucidation of mechanisms for pathogenesis and immunity in leishmaniasis. The aim of this study was to establish a murine model for human viscerotropic leishmaniasis, and the growth pattern of L. tropica was studied in different tissues of BALB/c mice in order to find out whether the parasite visceralizes in this murine model. L. major was used as a control as this species is known to cause a progressive infection in BALB/c mice. L. tropica or L. major was injected into the footpad of mice, and thickness of footpad, parasite loads in different tissues, and the weight of the spleen and lymph node were determined at different intervals. Results showed that L. tropica visceralizes to the spleen and grows there while its growth is controlled in footpad tissues. Dissemination of L. tropica to visceral organs in BALB/c mice was similar to the growth patterns of this parasite in human viscerotropic leishmaniasis. The BALB/c model of L. tropica infection may be considered as a good experimental model for human diseases.     

Numerical analysis and comparison of flow fields in normal larynx and larynx with unilateral vocal fold paralysis

In this study, laryngeal flow fields are investigated and compared in normal larynx and models of larynx with unilateral vocal fold paralysis (UVFP). In paralytic models, three fixed initial glottal gaps are considered to understand the positive or probable negative impacts of surgical operation on unilaterally paralytic larynx, by which the paralyzed vocal fold is brought closer to the mid-plane. Various features of the flow fields have been discussed in detail including glottal gap width, glottal flow rate, glottal exit pressure pattern and glottal jet evolution. The numerical solution of fluid-structure interaction is carried out using ANSYS, and the results confirm some of the favorable effects of surgery on the patient’s larynx. It is also shown that by tightening the glottal gap, some of the problems caused by the presence of a motionless vocal fold, such as leakage through glottal gap in the closure phase resulting in breathy voice can be moderated, although some of the symptoms of this disorder remain relatively unchanged.     

A comparison of postoperative outcomes with PDA ligation in the OR versus the NICU: a retrospective cohort study on the risks of transport

Background

Although patent ductus arteriosus (PDA) ligations in the Neonatal Intensive Care Unit (NICU) have been an accepted practice, many are still performed in the Operating Room (OR). Whether avoiding transport leads to improved perioperative outcomes is unclear. Here we aimed to determine whether PDA ligations in the NICU corresponded to higher risk of surgical site infection or mortality and if transport was associated with worsened perioperative outcomes.

Methods

We performed a retrospective cohort study of NICU patients, ≤37?weeks post-menstrual age, undergoing surgical PDA ligation in the NICU or OR. We excluded any infants undergoing device PDA closure. We measured the incidence of perioperative hypothermia, cardiac arrest, decreases in SpO2, hemodynamic instability and postoperative surgical site infection, sepsis and mortality.

Results

Data was collected on 189 infants (100 OR, 89 NICU). After controlling for number of preoperative comorbidities, weight at time of procedure, procedure location and hospital in the mixed-effect model, no significant difference in mortality or sepsis was found (odds ratio 0.31, 95%CI 0.07, 1.30; p?=?0.107, and odds ratio 0.40; 95%CI 0.14, 1.09; p?=?0.072, respectively). There was an increased incidence of hemodynamic instability on transport postoperatively in the OR group (12.4% vs 2%, odds ratio 6.93; 95% CI 1.48, 35.52; p?=?0.014).

Conclusion

PDA ligations in the NICU were not associated with higher incidences of surgical site infection or mortality. There was an increased incidence of hemodynamic instability in the OR group on transport back to the NICU. Larger multicenter studies following long-term outcomes are needed to evaluate the safety of performing all PDA ligations in the NICU.

Keywords

Patent ductus arteriosus, Newborn infant, Neonatal intensive care unit, Surgical wound infection, Postoperative period, Hemodynamics

     

Dall's sheep horn growth and harvest management in the Mackenzie Mountains,Northwest Territories,Canada

Across most of their native North American range, the horns of mountain sheep (Ovis spp.) males are getting smaller, a pattern attributed to selective hunting pressure. We measured the horns of 755 Dall's sheep males (Ovis dalli dalli) in the southern Mackenzie Mountains, Northwest Territories, between 2002 and 2017. For each male, we measured the circumference and length of each annulus for the right horn and calculated horn volume for each year. We examined changes in horn size in 4 different outfitter areas, using age at harvest as a covariate. Hunting pressure across years in the study area was consistently low, and this population did not experience the decline in horn size observed in several other mountain sheep populations in Canada. Over the 16-year period, the average horn volume of harvested males was stable and even increased in 1 outfitter area. Local management of Dall's sheep delivered independently by the guide outfitters in the Mackenzie Mountains appears to contribute to maintaining a population of males that has not been adversely affected by strong selective hunting pressure. The resilience of this management strategy may be challenged by environmental changes associated with rapid warming in northern mountain environments.     

Real-Time Effects of N-Methyl-d-Aspartic Acid on Dopamine Release in Slices of Rat Caudate Putamen: A Study Using Fast Cyclic Voltammetry

Abstract: The functional role of N-methyl-d -aspartic acid (NMDA) glutamate receptors in the real-time regulation of single electrical pulse (1 p)-stimulated endogenous dopamine release was investigated in slices of rat caudate putamen using fast cyclic voltammetry at a carbon fibre electrode. In the presence of Mg²⁺, 20 µM NMDA had a weak effect on background signals but did not affect 1 p-stimulated dopamine release. Removal of Mg²⁺ increased the background and doubled 1 p-stimulated dopamine release. In the absence of Mg²⁺, 20 µM NMDA caused a transient “release” of dopamine and decreased the background signal. The 1 p-stimulated dopamine release was subsequently reduced. In the presence of 1 µM (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), superfusion with 20 µM NMDA did not cause a transient “release” of dopamine, and 1 p-stimulated dopamine release was not subsequently attenuated. In the presence of 1 µM tetrodotoxin, 1 p-stimulated dopamine release was abolished, but 20 µM NMDA still caused a transient “release” of dopamine. Removal of Ca²⁺ from the artificial CSF abolished 1 p-stimulated dopamine release and resulted in a decline in the baseline but did not affect dopamine “release” when 20 µM NMDA was added. The dopamine release-inducing effect of 20 µM NMDA was less pronounced in sites in the caudate putamen where dopamine release increased with frequency of electrical stimulation (hot spots) than in sites where there was little frequency-dependent dopamine release (cold spots). Subsequent 1 p-stimulated dopamine release was less attenuated in cold spots than in hot spots. We conclude that in the absence of Mg²⁺, NMDA induces release of dopamine by acting at CPP-sensitive NMDA receptors in a Ca²⁺-independent manner. This transient release depletes dopamine from a storage site from which dopamine is released by 1 p electrical stimulation. These real-time observations of the effects of NMDA on electrical stimulus-independent and -dependent dopamine release may explain the apparently conflicting observations of the effects of NMDA on dopamine release made in previous studies. They also indicate that dopamine release and storage are heterogeneous at different sites in the rat caudate putamen.     

Pramipexole protects against apoptotic cell death by non-dopaminergic mechanisms

We have investigated the ability of pramipexole, a dopamine agonist used in the symptomatic treatment of Parkinson's disease (PD), to protect against cell death induced by 1-methyl-4-phenylpyridinium (MPP+) and rotenone in dopaminergic and non-dopaminergic cells. Pre-incubation with either the active (-)- or inactive (+)-enantiomer forms of pramipexole (10 microm) decreased cell death in response to MPP+ and rotenone in dopaminergic SHSY-5Y cells and in non-dopaminergic JK cells. The protective effect was not prevented by dopamine receptor blockade using sulpiride or clozapine. Protection occurred at concentrations at which pramipexole did not demonstrate antioxidant activity, as shown by the failure to maintain aconitase activity. However, pramipexole reduced caspase-3 activation, decreased the release of cytochrome c and prevented the fall in the mitochondrial membrane potential induced by MPP+ and rotenone. This suggests that pramipexole has anti-apoptotic actions. The results extend the evidence for the neuroprotective effects of pramipexole and indicate that this is not dependent on dopamine receptor occupation or antioxidant activity. Further evaluation is required to determine whether the neuroprotective action of pramipexole is translated to a disease-modifying effect in PD patients.     

Protective immunity against Leishmania major induced by Leishmania tropica infection of BALB/c mice

Leishmania (L.) tropica is a causative agent of human cutaneous and viscerotropic leishmaniasis. Immune response to L. tropica in humans and experimental animals are not well understood. We previously established that L. tropica infection induces partial protective immunity against subsequent challenge infection with Leishmania major in BALB/c mice. Aim of the present study was to study immunologic mechanisms of protective immunity induced by L. tropica infection, as a live parasite vaccine, in BALB/c mouse model. Mice were infected by L. tropica, and after establishment of the infection, they were challenged by L. major. Our findings shows that L. tropica infection resulted in protection against L. major challenge in BALB/c mice and this protective immunity is associated with: (1) a DTH response, (2) higher IFN-γ and lower IL-10 response at one week post-challenge, (3) lower percentage of CD4⁺ lymphocyte at one month post-challenge, and (4) the source of IFN-γ and IL-10 were mainly CD4⁻ lymphocyte up to one month post-challenge suggesting that CD4⁻ lymphocytes may be responsible for protection induced by L. tropica infection in the studied intervals.     

Array CGH using whole genome amplification of fresh-frozen and formalin-fixed, paraffin-embedded tumor DNA

The ability to utilize formalin-fixed, paraffin-embedded (FFPE) archival specimens reliably for high-resolution molecular genetic analysis would be of immense practical application in the study of human disease. We have evaluated the ability of the GenomePlex whole genome amplification (WGA) kit to amplify frozen and FFPE tissue for use in array CGH (aCGH). GenomePlex gave highly representative data compared with unamplified controls both from frozen material (Pearson's R(2) = 0.898) and from FFPE (R(2) = 0.883). Artifactual amplification observed using DOP-PCR at chromosomes 1p, 3, 13q, and 16p was not seen with GenomePlex. Highly reproducible aCGH profiles were obtained using as little as 5 ng starting material from FFPE (R(2) = 0.918). This WGA method should readily lend itself to the determination of DNA copy number alterations from small fresh-frozen and FFPE clinical tumor specimens, although some care must be taken to optimize the DNA extraction procedure.