scholarly journals In situ enhancement of pulmonary surfactant function using temporary flow reversal

2012 ◽  
Vol 112 (1) ◽  
pp. 149-158 ◽  
Author(s):  
Henry W. Glindmeyer ◽  
Bradford J. Smith ◽  
Donald P. Gaver

Acute respiratory distress syndrome is a pulmonary disease with a mortality rate of ∼40% and 75,000 deaths annually in the United States. Mechanical ventilation restores airway patency and gas transport but leads to ventilator-induced lung injury. Furthermore, surfactant replacement therapy is ineffective due to surfactant delivery difficulties and deactivation by vascular proteins leaking into the airspace. Here, we demonstrated that surfactant function can be substantially improved (up to 50%) in situ in an in vitro pulmonary airway model using unconventional flows that incorporate a short-term retraction of the air-liquid interface, leading to a net decrease in cellular damage. Computational fluid dynamic simulations provided insights into this method and demonstrated the physicochemical hydrodynamic foundation for the improved surfactant microscale transport and mobility. This study may provide a starting point for developing novel ventilation waveforms to improve surfactant function in edematous airways.

2012 ◽  
Vol 9 (74) ◽  
pp. 2201-2212 ◽  
Author(s):  
Vincenzo Guarino ◽  
Francesco Urciuolo ◽  
Marco A. Alvarez-Perez ◽  
Benedetto Mele ◽  
Paolo A. Netti ◽  
...  

The development of composite scaffolds with well-organized architecture and multi-scale properties (i.e. porosity, degradation) represents a valid approach for achieving a tissue-engineered construct capable of reproducing the medium- and long-term in vitro behaviour of hierarchically complex tissues such as spongy bone. To date, the implementation of scaffold design strategies able to summarize optimal scaffold architecture as well as intrinsic mechanical, chemical and fluid transport properties still remains a challenging issue. In this study, poly ɛ -caprolactone/polylactid acid (PCL/PLA) tubular devices (fibres of PLA in a PCL matrix) obtained by phase inversion/salt leaching and filament winding techniques were proposed as cell instructive scaffold for bone osteogenesis. Continuous fibres embedded in the polymeric matrix drastically improved the mechanical response as confirmed by compression elastic moduli, which vary from 0.214 ± 0.065 to 1.174 ± 0.143 MPa depending on the relative fibre/matrix and polymer/solvent ratios. Moreover, computational fluid dynamic simulations demonstrated the ability of composite structure to transfer hydrodynamic forces during in vitro culture, thus indicating the optimal flow rate conditions that, case by case, enables specific cellular events—i.e. osteoblast differentiation from human mesenchymal stem cells (hMSCs), mineralization, etc. Hence, we demonstrate that the hMSC differentiation preferentially occurs in the case of higher perfusion rates—over 0.05 ml min –1 —as confirmed by the expression of alkaline phosphate and osteocalcin markers. In particular, the highest osteopontin values and a massive mineral phase precipitation of bone-like phases detected in the case of intermediate flow rates (i.e. 0.05 ml min –1 ) allows us to identify the best condition to stimulate the bone extracellular matrix in-growth, in agreement with the hydrodynamic model prediction. All these results concur to prove the succesful use of tubular composite as temporary device for long bone treatment.


1994 ◽  
Vol 77 (6) ◽  
pp. 2899-2906 ◽  
Author(s):  
P. Navalesi ◽  
P. Hernandez ◽  
D. Laporta ◽  
J. S. Landry ◽  
F. Maltais ◽  
...  

In situ measurement of distal tracheal pressure (Ptr) via an intraluminal side-hole catheter (IC) has been used to determine endotracheal tube (Rett) and intrinsic patient (Rpt) resistances in intubated subjects. Because of differences in cross-sectional area between the endotracheal tube (ETT) and trachea, fluid dynamic principles predict that IC position should critically influence these results. Accordingly, the aim of this study was to determine the effect of IC position on Rett. Ptr was recorded in vitro through an IC from 2 cm inside, at the tip of, or 2 cm outside an ETT (7, 8, and 9 mm ID) situated within an artificial trachea (13, 18, and 22 mm ID). A reference value of Rett was also obtained. Results were unaffected by IC position during inspiration, overestimating Rett by 7.9 +/- 0.7% (SE). In contrast, during expiration, Rett fell as IC position changed from outside to inside the ETT and was underestimated by 41.3 +/- 3.6% with Ptr recorded inside the ETT. Varying ETT or tracheal size had little effect on the relative error in Rett. The IC itself did increase Rett due to a reduction in effective cross-sectional area, the change varying directly with IC size and inversely with ETT caliber. In vivo values in 11 intubated patients were comparable to in vitro results. In summary, IC position and size can have important consequences on in situ measurements of Ptr and should be considered when clinically monitoring Rett or Rpt.


1998 ◽  
Vol 550 ◽  
Author(s):  
D. Knaack ◽  
D.D. Lee

Abstractα-BSM™ is an injectable endothermically setting calcium phosphate bone substitute. α-BSM™ has been shown to be effective in promoting the healing of surgically created critical size defects and restoring bone biomechanical strength in several animal models. It has received regulatory clearance for orthopedic indications in both Canada and Europe and for dental and craniofacial indications in the United States.α-BSM™ is distinguished as a bone substitute by its prolonged working time at room temperature, and rapid hardening at body temperature. These properties, as well as its compatibility with a variety of aqueous hydrating agents, make α-BSM™ an attractive vehicle for the in situ delivery of therapeutic agents. In vitro studies have shown that antibiotics, such as gentamicin, can be stably incorporated into α-BSM™ prior to and during hardening, and that delivery kinetics can be controlled with the appropriate formulation and preparative procedures. The setting reaction is also compatible with biologically active proteins. rhBMP-2 has been incorporated into α-BSM™ and was demonstrated to be effective in stimulating ectopic bone formation in soft tissue and accelerating the restoration of a differentiated phenotype in a rabbit osteotomy model.


Biofilms ◽  
2004 ◽  
Vol 1 (1) ◽  
pp. 5-12 ◽  
Author(s):  
J. S. Foster ◽  
P. C. Pan ◽  
P. E. Kolenbrander

Oral bacteria form mixed-species biofilms known as dental plaque. Growth of these complex microbial communities is often controlled with the use of antimicrobial mouthrinses. Novel laboratory methods for testing the efficacy of antimicrobials in situ are necessary to complement current clinical testing protocols. In this study, we examined the effects of antimicrobial agents on a streptococcal biofilm grown in a saliva-conditioned flowcell. The flowcell coupled with confocal laser scanning microscopy enabled examination of growing oral biofilms in situ without disruption of the microbial community. Biofilms composed of Streptococcus gordonii DL1 were grown in an in vitro flowcell and treated with several commercially available antimicrobial mouthrinses containing essential oils, triclosan, cetylpyridinium chloride/domiphen or chlorhexidine. The results of this study revealed varying abilities of the antimicrobial agents to cause cellular damage on the growing biofilm in situ. This study therefore demonstrated the usefulness of the flowcell in the rapid assessment of antimicrobial efficacy.


2012 ◽  
Vol 78 (15) ◽  
pp. 5104-5110 ◽  
Author(s):  
Matilde Fernández ◽  
José Luis Niqui-Arroyo ◽  
Susana Conde ◽  
Juan Luis Ramos ◽  
Estrella Duque

ABSTRACTIn this work, we explore the potential use of thePseudomonas putidaKT2440 strain for bioremediation of naphthalene-polluted soils.Pseudomonas putidastrain KT2440 thrives in naphthalene-saturated medium, establishing a complex response that activates genes coding for extrusion pumps and cellular damage repair enzymes, as well as genes involved in the oxidative stress response. The transfer of the NAH7 plasmid enables naphthalene degradation byP. putidaKT2440 while alleviating the cellular stress brought about by this toxic compound, without affecting key functions necessary for survival and colonization of the rhizosphere.Pseudomonas putidaKT2440(NAH7) efficiently expresses the Nah catabolic pathwayin vitroandin situ, leading to the complete mineralization of [14C]naphthalene, measured as the evolution of14CO2, while the rate of mineralization was at least 2-fold higher in the rhizosphere than in bulk soil.


Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2059
Author(s):  
Fangyu Du ◽  
Qifan Zhou ◽  
Wenjiao Sun ◽  
Cheng Yang ◽  
Chunfu Wu ◽  
...  

5-Hydroxyindole derivatives have various demonstrated biological activities. Herein, we used 5-hydroxyindole as a synthetic starting point for structural alterations in a combinatorial process to synthesize 22 different compounds with EZH2 inhibitor pharmacophores. A series of 5-hydroxyindole-derived compounds were screened inhibitory activities against K562 cells. According to molecular modeling and in vitro biological activity assays, the preliminary structure-activity relationship was summarized. Compound L–04 improved both the H3K27Me3 reduction and antiproliferation parameters (IC50 = 52.6 μM). These findings revealed that compound L–04 is worthy of consideration as a lead compound to design more potent EZH2 inhibitors. During the preparation of compounds, we discovered that trichloroisocyanuric acid (TCCA) is a novel catalyst which demonstrates condensation-promoting effects. To gain insight into the reaction, in situ React IR technology was used to confirm the reactivity. Different amines were condensed in high yields with β-diketones or β-ketoesters in the presence of TCCA to afford the corresponding products in a short time (10~20 min), which displayed some advantages and provided an alternative condensation strategy.


Author(s):  
Denise McAloose ◽  
Melissa Laverack ◽  
Leyi Wang ◽  
Mary Lea Killian ◽  
Leonardo C. Caserta ◽  
...  

AbstractWe describe the first cases of natural SARS-CoV-2 infection detected in animals in the United States. In March 2020, four tigers and three lions at the Bronx Zoo developed mild respiratory signs. SARS-CoV-2 RNA was detected by rRT-PCR in respiratory secretions and/or feces from all seven affected animals; viral RNA and/or antibodies were detected in their keepers. SARS-CoV-2 was isolated from respiratory secretions or feces from three affected animals; in situ hybridization co-localized viral RNA with cellular damage. Whole genome sequence and haplotype network analyses showed tigers and lions were infected with two different SARS-CoV-2 strains, suggesting independent viral introductions. The source of SARS-CoV-2 infection in the lions is unknown. Epidemiological data and genetic similarities between keeper and tiger viruses indicate human to animal transmission.


Author(s):  
J. P. Revel

Movement of individual cells or of cell sheets and complex patterns of folding play a prominent role in the early developmental stages of the embryo. Our understanding of these processes is based on three- dimensional reconstructions laboriously prepared from serial sections, and from autoradiographic and other studies. Many concepts have also evolved from extrapolation of investigations of cell movement carried out in vitro. The scanning electron microscope now allows us to examine some of these events in situ. It is possible to prepare dissections of embryos and even of tissues of adult animals which reveal existing relationships between various structures more readily than used to be possible vithout an SEM.


Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.


Author(s):  
A. Hakam ◽  
J.T. Gau ◽  
M.L. Grove ◽  
B.A. Evans ◽  
M. Shuman ◽  
...  

Prostate adenocarcinoma is the most common malignant tumor of men in the United States and is the third leading cause of death in men. Despite attempts at early detection, there will be 244,000 new cases and 44,000 deaths from the disease in the United States in 1995. Therapeutic progress against this disease is hindered by an incomplete understanding of prostate epithelial cell biology, the availability of human tissues for in vitro experimentation, slow dissemination of information between prostate cancer research teams and the increasing pressure to “ stretch” research dollars at the same time staff reductions are occurring.To meet these challenges, we have used the correlative microscopy (CM) and client/server (C/S) computing to increase productivity while decreasing costs. Critical elements of our program are as follows:1) Establishing the Western Pennsylvania Genitourinary (GU) Tissue Bank which includes >100 prostates from patients with prostate adenocarcinoma as well as >20 normal prostates from transplant organ donors.


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