Dynamic eye misalignment retroversion system (DEMRS)

Strabismus is a medical term used to define the eye misalignment conditions that prevent both eyes from focusing on the same target simultaneously. This is a disability that prohibits the perception of depth. The purpose of going through treatment is to realign the bad (strabismic) eye, so that it fixates on the same target as the good (correct) eye. This paper presents a novel system that can dynamically adjust the light rays coming into each eye in order to stimulate both foveae, with the correct image, simultaneously. This system is to be used in diagnosis and treatment for children with strabismus under the age of eight and for patients of any age suffering from Convergence Insufficiency (CI) or Diplopia

Role of the nitric oxide-soluble guanylyl cyclase pathway in obstructive airway diseases

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Guanylyl cyclase activation reverses resistive breathing–induced lung injury and inflammation

Inspiratory resistive breathing (RB), encountered in obstructive lung diseases, induces lung injury. The soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway is down-regulated in chronic and acute animal models of RB, such as asthma, chronic obstructive pulmonary disease, and in endotoxin-induced acute lung injury. Our objectives were to: (1) characterize the effects of increased concurrent inspiratory and expiratory resistance in mice via tracheal banding; and (2) investigate the contribution of the sGC/cGMP pathway in RB-induced lung injury. Anesthetized C57BL/6 mice underwent RB achieved by restricting tracheal surface area to 50% (tracheal banding). RB for 24 hours resulted in increased bronchoalveolar lavage fluid cellularity and protein content, marked leukocyte infiltration in the lungs, and perturbed respiratory mechanics (increased tissue resistance and elasticity, shifted static pressure–volume curve right and downwards, decreased static compliance), consistent with the presence of acute lung injury. RB down-regulated sGC expression in the lung. All manifestations of lung injury caused by RB were exacerbated by the administration of the sGC inhibitor, 1H-[1,2,4]oxodiazolo[4,3-]quinoxalin-l-one, or when RB was performed using sGCα1 knockout mice. Conversely, restoration of sGC signaling by prior administration of the sGC activator BAY 58-2667 (Bayer, Leverkusen, Germany) prevented RB-induced lung injury. Strikingly, direct pharmacological activation of sGC with BAY 58-2667 24 hours after RB reversed, within 6 hours, the established lung injury. These findings raise the possibility that pharmacological targeting of the sGC–cGMP axis could be used to ameliorate lung dysfunction in obstructive lung diseases

Dynamic Retroversion of Strabismus

Strabismus is a medical term used to define eye misalignment conditions that prevent both eyes from focusing on the same target simultaneously. Apart from having an aesthetic impact on the subject, strabismus is a dis- ability that prohibits the correct perception of depth. The purpose of going through treatment is to realign the “bad" (strabismic) eye, so that it fixates on the same target as the “good" (dominant) eye. This research presents a novel system called Dynamic Eye Misalignment Retroversion System (DEMRS), that can dynamically adjust the light rays coming into each eye, such that both foveae are stimulated by the same target, simultaneously. To test the system, a simulated implementation was created using a set of strabismus cases for known targets. The simulated results show, that the system is able to re-align both light rays such that they intersect the target successfully. Fur- thermore, a research prototype was built to assess the efficacy of the DEMRS in the successful fusion of the stimuli coming into each eye, from the correct target, simultaneously. The clinical evaluation experiments were conducted under lab conditions, using subjects with normal vision and strabismus, be- tween the ages of 8 and 98 years. Overall, 21 subjects underwent clinical evaluation and, in each experiment, the fusion success of both stimuli at near and far targets was recorded. The results indicate that the DEMRS is able to restore successfully the correct perception of depth, through binocu- lar vision, for young children, adults and elders

Soluble guanylyl cyclase in ALI / ARDS caused by sepsis

Soluble guanylyl cyclase (sGC) is a cGMP generating enzyme implicated in the control of smooth muscle tone that also regulates platelet aggregation. Moreover, sGC activation has been shown to reduce leukocyte adherence to the endothelium. Herein, we investigated the expression of sGC in a murine model of LPS-induced lung injury and evaluated the effects of sGC inhibition in the context of acute lung injury (ALI). Lung tissue sGC α1 and β1 subunits protein levels were determined by western blot and immunohistochemistry, and steady-state mRNA levels for the β1subunit were assessed by real-time PCR. LPS inhalation resulted in a decrease in β1 mRNA levels, as well as a reduction in both sGC subunit protein levels. Decreased α1 and β1 expression was observed in bronchial smooth muscle and epithelial cells. Tumor necrosis factor-α (TNF-α) was required for the LPS-triggered reduction in sGC protein levels, as no change in α1 and β1 levels was observed in TNF-α knockout mice. To determine the effects of sGC blockade in LPS-induced lung injury, mice were exposed to ODQ prior to the LPS challenge. Such pretreatment led to a further increase in total cell number (mainly due to an increase in neutrophils) and protein concentration in the bronchoalveoalar lavage fluid; the effects of ODQ were reversed by a cell-permeable cGMP analogue. We conclude that sGC expression is reduced in LPS-induced lung injury, while inhibition of the enzyme with ODQ worsens lung inflammation, suggesting that sGC exerts a protective role in ALI. Keywords: endotoxin, cGMP, soluble guanylyl cyclase; acute lung injury Abstract Abbreviations: acute lung injury (ALI); bronchoalveolar lavage fluid (BALF); nitric oxide (NO); NO sysnthase (NOS); soluble-guanylyl-cyclase (sGC); lipopolysaccharide (LPS); Tumor Necrosis Factor (TNF) -α; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ); 8pCPTcGMP (8-(4-chlophenylthio)-guanosine 3,5 cyclic monophosphate) dimethyl sulfoxide (DMSO);Διαλυτή Γουανυλική Κυκλάση (δΓΚ) αποτελεί το ένζυμο για το σχηματισμό του cGMP, και εμπλέκεται στη ρύθμιση του τόνου των λείων μυών και τη συσσώρευση των αιμοπεταλίων. H ενεργοποίηση της δΓΚ έχει διαπιστωθεί ότι επιδρά αρνητικά στην προσκόλληση των ουδετερόφιλων κυττάρων στο ενδοθήλιο. Στην παρούσα μελέτη, διερευνήσαμε την έκφραση της δΓΚ σε πειραματικό μοντέλο οξείας πνευμονικής βλάβης, επιμύων που εισέπνευσαν εκνέφωμα ενδοτοξίνης και εκτιμήσαμε την επίδραση της αναστολής της δΓΚ στα πλαίσια του συνδρόμου ALI/ARDS. Χρησιμοποιώντας μεθόδους ανοσοτύπωσης κατά Western και ανοσοιστοχημείας μελέτησαμε τη συγκέντρωση πρωτεΐνης επίπεδα και με real time -PCR υπολογίσαμε τα επίπεδα mRNA των υπομονάδων α1 και β1 της δΓΚ στον πνευμονικό ιστό επιμύων του πειραματικού αυτού μοντέλου. Η εισπνοή ενδοτοξίνης είχε ως αποτέλεσμα τη μείωση του mRNA της β1 υπομονάδας, καθώς και τη μείωση των πρωτεϊνικών επιπέδων αμφότερων των υπομονάδων της δΓΚ. Η μειωμένη έκφραση των α1 και β1 υπομονάδων της δΓΚ παρατηρήθηκε επίσης και με ανοσοϊστοχημική ανάλυση, στα λεία μυικά κύτταρα και τα επιθηλιακά κύτταρα των βρόγχων του πνεύμονα των επιμύων. Επίσης διαπιστώθηκε ότι ο παράγοντας νέκρωσης όγκου (Tumor Necrosis Factor) - α, αποτελεί προυπόθεση για τη μείωση των πρωτεϊνικών επιπέδων της δΓΚ, καθώς δεν παρατηρείται καμία μεταβολή των υπομονάδων α1 και β1 σε διαγονιδιακά ποντίκια με ομόζυγη έλλειψη της κυτταροκίνης μετά την εισπνοή ενδοτοξίνης. Για να εξετάσουμε την επίδραση της αναστολής της ενζυμικής δράσης της δΓΚ, στην πνευμονική βλάβη από την εισπνοή ενδοτοξίνης, τα πειραματόζωα εκτέθηκαν στον ειδικό αναστολέα ODQ, προτού εισπνεύσουν τα εκνέφωμα ενδοτοξίνης. Η χορήγηση εισπνεόμενου ODQ οδήγησε σε περαιτέρω αύξηση του αριθμού των ουδετερόφιλων κυττάρων και της συγκέντρωσης πρωτεΐνης στο βρογχοκυψελιδικό έκπλυμα, επιτείνοντας τη φλεγμονή στον πνεύμονα, που προκαλείται από την εισπνοή ενδοτοξίνης. Τα αποτελέσματα αυτά ήταν δυνατό να αναστραφούν με τη χορήγηση ειδικού αναλόγου του cGMP. Συμπερασματικά στην παρούσα μελέτη διαπιστώσαμε ότι η έκφραση της δΓΚ μειώνεται στο πειραματικό μοντέλο επιμύων με οξεία πνευμονική βλάβη, μετά από εισπνοή ενδοτοξίνης, ενώ η αναστολή της ενζυμικής δράσης του, επιδεινώνει ακόμη περισσότερο την φλεγμονώδη βλάβη στον πνεύμονα. Τα αποτελέσματα αυτά υποδεικνύουν ένα προστατευτικό ρόλο της δΓΚ στην οξεία πνευμονική βλάβη στα πλαίσια του συνδρόμου ALI/ARDS. Συντομογραφίες περίληψης : Oξεία πνευμονική βλάβη: acute lung injury (ALI), Βρογχοκυψελιδικό έκπλυμα: bronchoalveolar lavage fluid (BALF), Μονοξείδιο του αζώτου: (NO), Συνθάση του ΝΟ: (NOS), διαλυτή γουανυλική κυκλάση : (δΓΚ), λιποπολυσακχαρίτης (LPS), Παράγοντας νέκρωσης όγκων-α: Tumor Necrosis Factor (TNF)-α, 1H-[1,2,4]οξαδιοζολο[4,3-a]κινοξαλίνη-1-ένα (ODQ), 8-(4-χλωροφαινύλθιο)- 3,5 κυκλική μονοφωσφορική γουανοσίνη: (8pCPTcGMP), Διμεθυλο σουλφοξίδιο: (DMSO)

The differential effects of inspiratory, expiratory, and combined resistive breathing on healthy lung

Combined resistive breathing (CRB) is the hallmark of obstructive airway disease pathophysiology. We have previously shown that severe inspiratory resistive breathing (IRB) induces acute lung injury in healthy rats. The role of expiratory resistance is unknown. The possibility of a load-dependent type of resistive breathing-induced lung injury also remains elusive. Our aim was to investigate the differential effects of IRB, expiratory resistive breathing (ERB), and CRB on healthy rat lung and establish the lowest loads required to induce injury. Anesthetized tracheostomized rats breathed through a two-way valve. Varying resistances were connected to the inspiratory, expiratory, or both ports, so that the peak inspiratory pressure (IRB) was 20%-40% or peak expiratory (ERB) was 40%-70% of maximum. CRB was assessed in inspiratory/expiratory pressures of 30%/50%, 40%/50%, and 40%/60% of maximum. Quietly breathing animals served as controls. At 6 hours, respiratory system mechanics were measured, and bronchoalveolar lavage was performed for measurement of cell and protein concentration. Lung tissue interleukin-6 and interleukin-1 beta levels were estimated, and a lung injury histological score was determined. ERB produced significant, load-independent neutrophilia, without mechanical or permeability derangements. IRB 30% was the lowest inspiratory load that provoked lung injury. CRB increased tissue elasticity, bronchoalveolar lavage total cell, macrophage and neutrophil counts, protein and cytokine levels, and lung injury score in a dose-dependent manner. In conclusion, CRB load dependently deranges mechanics, increases permeability, and induces inflammation in healthy rats. ERB is a putative inflammatory stimulus for the lung