Presynaptic terminals of neurons are optimized for neurotransmitter release, which is tightly controlled by presynaptic calcium. Here, we evaluate the role of calcium influx through voltage-gated calcium channels (VGCCs) in regulating the initial vesicular release probability (p) and the number of vesicles available for release by action potentials (effective RRP) at the calyx of Held synapse in mice. Two established methods of estimating effective RRP size and p reveal that both are calcium dependent. Reducing calcium influx by blocking R-type (VGCCs) or P/Q-type VGCCs also reduces EPSC amplitude via p and effective RRP size. Furthermore, activation of gamma-aminobutryic acid class B (GABAB) receptors, which reduces presynaptic calcium by regulating VGCCs without other significant effects on release, also reduces the effective RRP size and p. These findings suggest that the calcium dependence of RRP size may influence the manner in which certain neuromodulators affect neurotransmitter release.

I developed a system to release multiple growth factors from PEGylated fibrin gels with varying profiles to induce vasculogenesis from embedded human MSCs. Zero-order release can be obtained by conjugating a growth factor with a homobifunctional, amine-reactive, PEG derivative. Growth factors can be entrapped during thrombin-mediated crosslinking and released rapidly. Growth factors with physical affinity for fibrinogen or fibrin can be sequestered within the matrix and released via degradation and/or disassociation. PDGF-BB was loaded via entrapment while TGF-β1 was sequestered through a combination of physical affinity and conjugation. The affinity of TGF-β1 and fibrinogen had never been previously examined or quantified. I aimed to determine the Ka and Kd between TGF-β1 and fibrinogen through a variety of assays. Binding ELISAs were developed for TGF-β1 and fibronectin, a protein associated with fibrin gels, and TGF-β1 and fibrinogen. However, background was high due to insufficient blocking agents. Other assays explored included western blots, surface plasmon resonance, and radiolabeled TGF-β1 with limited success. The affect of TGF-β1 on human MSC differentiation towards vascular cell phenotypes was examined both in 2D and fibrin gels embedded with MSCs. With exposure to TGF-β1, MSC proliferation was significantly inhibited in both 2D and within fibrin gels indicating that loaded TGF-β1 maintained bioactivity for at least 7 days. Gene expression of MSCs exposed to TGF-β1 demonstrated inhibited endothelial cell differentiation and stimulated smooth muscle cell differentiation. However, confocal and light microscopy indicated that endothelial cell differentiation is maintained with TGF-β1 loaded PEGylated fibrin gels. The system developed is highly modular and can be applied to other tissue engineering systems. Furthermore, other growth factors could be incorporated to promote vascular cell differentiation. / text

The aim of this research was to develop and fully investigate a novel method of antibiotic drug delivery to the lung that will address problems with current therapeutic regimens for treatment of airway infections. To demonstrate the performance of prepared formulations, the design of suitable characterization methods were also aimed. A novel dissolution method for evaluating the in vitro dissolution behavior of inhalation formulations was developed. The membrane holder was designed to enclose previously air-classified formulations so that they could be uniformly tested in the dissolution apparatus. Dissolution procedures, the apparatus, the dose collection, the medium, and test conditions were developed and the dissolution behaviors of test compounds were evaluated by experimental and mathematical analysis. It was proved that the aerodynamic separation of formulation prior to dissolution assessment have a significant influence on the dissolution profiles. The optimized test method using the membrane holder was applied to evaluate in vitro dissolution profiles of the manufactured formulations of rifampicin (RF). The carrier/excipient-free RF dry powder formulation was investigated. The rifampicin dihydrate (RFDH) powders having MMAD of 2.2 um were prepared using a simple recrystallization process. The RFDH powders have a thin flaky structure, and this unique morphology provides improved aerosolization properties at maximal API loading. The manufactured RFDH formulation showed 80% drug release within 2 hours. To retard the release rate of RF, the prepared RFDH crystals were coated with hydrophobic polymer, PLA or PLGA, using spray-dryer equipped with multi-channel spray nozzles. The multi-channel spray nozzle used in this study has two separate nozzles for aqueous solution and one for gas fluid. The RFDH crystals and the coating solutions were sprayed through the two separate liquid nozzles at the same time. The coated RFDH formulations were prepared using multi-channel spray nozzles. The coated formulations contained at least 50% w/w of RF with no change of their flaky morphology. The initial RF release was lowered by coating; the lowest initial RF release was observed from the coated powders with PLA polymer as 32% among the coated formulations. Overall, the 80% of RF was released within 8 hours. The RFDH and coated RFDH formulations delivered via the pulmonary route would be anticipated to provide higher local (lung) drug concentrations than that of orally delivered powders. Particularly, the coated RFDH powders deposited in the alveolar region may prolong the drug residence time in the site of infections. Additionally, it was proved that the RFDH and coated RFDH formulations provided much better stability than the amorphous RF. / text

The primary purpose of this study was to observe the relationship between muscle activation of the right hand with the force produced at the fingertips in an isometric precision pinch tracking task. Thirty right-handed subjects, 15 males and 15 females, with a mean age 23.5 (SD 3.5) years, free from any neurological disorder or physical ailment, had a pair of electromyography (EMG) electrodes placed over the first dorsal interosseous (FDI) muscle, which acts on the index finger, while performing a pinch force tracking task scaled to 20% maximum voluntary contraction (MVC). The tracking task was chosen because it created a continuously increasing force application to 20% MVC and then decreasing force release from 20% MVC at a prescribed rate in both cases of 6.66% MVC force per second. In addition to showing increases in EMG activation of the FDI with increases in force, the results revealed that muscle activation for a given force level was generally greater for force application than for force release. This may be due dynamics of muscle contraction or to patterns of multiple muscle coordination. / text

Η παρούσα εργασία μελετά την ανάπτυξη ενός ευέλικτου συστήματος αντιμικροβιακής προστασίας για εφαρμογή σε είδη ρουχισμού και υφάσματα οικιακής χρήσης. Πιο συγκεκριμένα αναπτύχθηκαν διασυνδεδεμένα πολυμερικά νανοσφαιρίδια πολυστυρολίου-διβινυλοβενζολίου στα οποία ενσωματώθηκε Triclosan, μία ευρέος φάσματος εμπορική αντιμικροβιακή ουσία. Σημειώνεται ότι στο πλαίσιο ανάσχεσης των ενδονοσοκομειακών λοιμώξεων η ανάπτυξη αντιμικροβιακών νοσοκομειακών στολών, σεντονιών και άλλων σχετικών κλωστοϋφαντουργικών προϊόντων αποτελούν τις τελευταίες δεκαετίες αντικείμενο έντονου επιστημονικού ενδιαφέροντος. Το μέγεθος των νανοσωματιδίων βρέθηκε μετά από εξέταση με ηλεκτρονική μικροσκοπία σάρωσης (SEM) και δυναμική σκέδαση φωτός (DLS) να κυμαίνεται μεταξύ 35-350 nm ανάλογα την σύσταση. H θερμική συμπεριφορά τους μελετήθηκε μέσω διαφορικής θερμιδομετρίας σάρωσης (DSC) και διαπιστώθηκε σημείο τήξεως στους ~425 οC. Χρησιμοποιώντας την φασματοσκοπία UVVis προσδιορίστηκε ο πραγματικός εγκλωβισμός του αντιμικροβιακού στο σύστημα κατά μέσο όρο σε ποσοστό ~72% του ονομαστικού και παρακολουθήθηκε ο ρυθμός αποδέσμευσης του σε διαλύματα αιθανόλης-νερού. Επιπλέον, τα σφαιρίδια που όπως διαπιστώθηκε παρουσιάζουν χαρακτηριστικά ελεγχόμενης αποδέσμευσης ενσωματώθηκαν σε μήτρες πολυπροπυλενίου οι οποίες υπό την μορφή φιλμ εφελκύστηκαν μονοαξονικά. Τέλος κάνοντας χρήση της δονητικής φασματοσκοπίας Raman εκτιμήθηκε ο μοριακός προσανατολισμός που επιβλήθηκε στα εφελκυσμένα φιλμ και συσχετίσθηκε με την παρατηρούμενη μείωση που επιτεύχθηκε στην κινητική αποδέσμευσης της εγκλωβισμένης δραστικής ουσίας. Το πρώτο κεφάλαιο της παρούσας εργασίας ασχολείται με το πρόβλημα της μικροβιακής επιμόλυνσης υφασμάτων, τις διάφορες λύσεις που έχουν προταθεί κατά καιρούς και τέλος αναλύει τον στόχο της παρούσας εργασίας. Στο δεύτερο κεφάλαιο επεξηγείται η έννοια της ελεγχόμενης αποδέσμευσης και περιγράφονται οι διάφορες κατηγορίες συστημάτων ελεγχόμενης χορήγησης μαζί με χαρακτηριστικά παραδείγματα. Τα νανοσωματίδια, η σύστασή, οι μοναδικές ιδιότητες, οι εφαρμογές και οι διάφοροι τρόποι σύνθεσης και χαρακτηρισμού τους συζητούνται στο τρίτο κεφάλαιο. Το τέταρτο κεφάλαιο αναφέρει πληροφορίες για τα υλικά και επεξηγεί τις τεχνικές που χρησιμοποιήθηκαν στην σύνθεση, την επεξεργασία και τον χαρακτηρισμό των νανοσωματιδίων και των μιγμάτων τους. Τέλος στο πέμπτο κεφάλαιο παρουσιάζονται τα αποτελέσματα των πειραμάτων που πραγματοποιήθηκαν και ακολουθεί ο σχολιασμός τους. / The present thesis studies the development of a versatile system of antimicrobial protection for use in clothing and household products. In particular Triclosan incorporated crosslinked polystyrenedinylbenzene nanobeads were developed; triclosan is a widely used antimicrobial agent. It is noted that the health hazards arising during nosocomial treatment due to infections caused by microbial pathogens and the means to protect oneself against such threats have become the subject of many research activities during the last few decades. The size of the nanoparticles after examination with scanning electron microcopy (SEM) and dynamic light scattering (DLS) was found to vary between 35-350 nm depending on the system formulation. Their thermal behavior was studied with differential scanning calorimetry (DSC) and their melting point was measured at ~425 oC. Using UV-Vis spectroscopy the real encapsulation efficiency of the antimicrobial in the system was determined at ~72% and its release kinetics were studied in a water-ethanol solution. The nanobeads possess controlled release properties; they were furthermore incorporated into polypropylene matrixes which were uniaxially drawn in film form. Finally utilizing polarized Raman spectra, the draw induced molecular orientation of the films was correlated to the relevant variation of the related antimicrobial release kinetics. The first chapter of the present thesis reviews the textile microbial infections and the various solutions that have been proposed showing up the specific research goal targeted. In the second chapter the meaning of controlled release is explained and the basic system categories involved are presented along with characteristic examples. The nanoparticles, their composition, special attributes, applications, synthesis and characterization techniques are the subject of the third chapter. The fourth chapter reports information about the materials and the methods used in the synthesis, postprocessing and characterization of the nanoparticles and their blends. Finally the last chapter presents the experimental results and relevant comments.

The traditional lands of the Southern Paiute people are bounded by more than 600 miles of Piapaxa (Colorado River) from the Kaiparowits Plateau in the north to Blythe, California in the south. According to traditional beliefs, Southern Paiute people were created in this traditional land and, through this creation, the Creator gave Paiute people a special supernatural responsibility to protect and manage this land including its water and natural resources. Puaxantu Tuvip (sacred land) is the term that refers to traditional ethnic territory. Within these lands no place was more special than Piapaxa 'uipi (Big River Canyon) where the Colorado River cuts through the Grand Canyon.

Controlled release formulations offer many advantages over conventional dosage forms. These include reduced plasma fluctuations and improved patient comp1i:nce. Complex controlled release formulations such as those with enteric release properties, often require additional steps in the production phase. The costs and economic impact associated with these complex controlled release dosage formulations often outweigh the immediate benefits. Thus the development of an economic method to produce controlled release particles is of great importance especially in third world countries. In controlled release formulations, the drug is generally dispersed throughout a polymer matrix. The rate of drug release is often determined by the viscosity or complexity of the polymer matrix through which the drug needs to diffuse in order to be released. With enteric release the polymer coating, insoluble in an acidic environment is often applied in the final phase of production. Chitosan is a versatile polymer of natural origin with many favourable characteristics. These include its safety, biocompatibility, and biodegradability. Simple methods can be applied and modified to produce controlled release particles form chitosan. The effect of modern controlled release polymers such as Aqoat AS-HF, Eudragit SlOO and Kollidon SR was investigated. Chitosan beads and chitosan-polymer beads, as well as chitosan granules and chitosan-polymer granules, were prepared and investigated as possible controlled release formulations. Ketoprofen was chosen as the model drug. Chitosan beads and chitosan-polymer beads were prepared by inotropic gelation in tripolyphosphate. Chitosan granules and chitosan-polymer matrix granules were prepared by binding chitosan with an acetic acid solution as a granulating system. The beads and granules appeared differed in appearance as well as in the results obtained from various experiments. Granules prepared in the study did not appear to be effective with regards to enteric and controlled release. Beads prepared form Kollidon SR appeared to be effective with regards to enteric and controlled release, with Kollidon 1% and 5% w/v chitosan beads achieving good drug loading of up to 73.13% and releasing less than 15 % of the total drug content in 0.1 M HCI after 60 minutes. Drug release continued steadily for up to 360 minutes in pH 7.2. It was concluded that Kollidon SR loaded chitosan beads nay be a viable controlled release dosage form with enteric release properties, and that future experiments, possibly with lower polymer concentrations, are worthwhile / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.

The physiological responses to stressor exposure can be broadly grouped into the organismal and the cellular stress responses. The organismal stress response involves the release of hormones into general circulation, while the cellular stress response involves the synthesis of proteins, the most important being the heat shock proteins (HSPs), which play a role in maintaining protein homeostasis. Elevated HSP70 expression in response to stressors has been demonstrated in trout (Oncorhynchus mykiss) red blood cells (RBCs). The ease of repeated sampling of blood suggests the possibility of using this tissue as a non-lethal marker of cellular stress in fish. This study tested the hypothesis that stressor exposure will elevate HSP70 expression in trout RBCs and the role of stress hormones in mediating this response. Acute heat shock exposure (+12oC) significantly elevated plasma cortisol, glucose and lactate levels in heat shocked fish over 24 h. A tissue-specific response was seen in HSP70 expression in liver, brain, gill and RBCs. To enable measurement of RBC HSP70 concentrations, an enzyme-linked immunosorbent assay (ELISA) was developed using a commercially available rabbit anti-salmon HSP70 and a recombinant chinook salmon (Oncorhynchus tshawytscha) HSP70. To determine effects of chronic exposure, two studies were conducted exposing trout to either cadmium (0, 0.75 or 2.0 µg/L over 28 d) or municipal wastewater effluent (0, 20 or 90% over 14 d). However, neither exposure elicited a significant HSP70 response. Effects of stress hormones on RBC HSP70 levels were tested by exposing cells in vitro to either cortisol (10 and 100 ng/mL) or epinephrine (10 nM) with or without heat shock. Heat shock elevated HSP70 content in trout RBCs but no modulation by stress hormones was seen. It was shown for the first time that RBCs release HSP70 content into the medium in response to an acute heat shock and this release is attenuated by stress hormones. Overall, HSP70 levels in RBCs have the potential to be a reliable non-lethal marker of acute cellular stress effects in fish. The release of HSP70 from RBCs leads to the hypothesis that HSP70 may also have an extracellular role in fish, and warrants further study.

Background: Two-year nationwide prison recidivism rates stand at over 60%, and minorities and the poor are at greatest risk both of first-time incarceration and of offending repeatedly over time. Initiatives that may address prison inmates’ lack of resources and increase their success in their communities after release are now an important topic in the study of criminal justice policy. Over the course of the past two decades, the public health concern of HIV/AIDS has increasingly become a part of this discourse on re-entry, as the disease disproportionately affects minority communities both in and outside of prisons. Affected reentrants face not only the challenges associated with employment, education, housing, and other social infrastructure that impede their long-term re-entry into mainstream society, but must also navigate issues surrounding continuity of medical care and behavioral risk reduction. In 2009, Georgia State University received funding to conduct an evaluation of Georgia’s Pre-Release Planning Program (PRPP) for HIV-positive inmates, and conducted semi-structured interviews with 25 former inmates who had received services from PRPP. This thesis work attempts to assess the content of the interviews and the potential impact of such an evaluation on corrections policy, especially in light of other similar programs that have been funded nationwide. Methods: A literature review was conducted to provide information on state and Federal pre-release programs for HIV+ prisoners that have been funded since the 1990s. A qualitative analysis of the GSU interview transcripts, consisting of coding for major themes, was completed. The goal of the analysis was to determine what program components had been most beneficial to participants, and also what needs had gone unfulfilled. Results: Most participants (23/25) in receipt of pre-release planning services in Georgia felt that they had benefitted from the program. A majority (19/25) attended the appointments set up for them by the program coordinator. Respondents were generally satisfied with their medical care, though cases existed where respondents had been unable to access a stable provider or medication supply as planned. The greatest aid to participants from PRPP was in the area of medical care. Limitations were perceived in the areas of employment after release and the Department of Labor program to which PRPP referred participants, as well as housing to a lesser degree. Study participants acknowledged and appreciated the program coordinator’s hard work with the resources that she had, and recommended transitional housing and work programs as ideal resources to improve their situations. Almost all (22/23) expressed interest in a community mentoring program to aid their progress post-release. Conclusions: Literature showed a variety of education and prevention program models targeting HIV in prisons since the 1990s. The best program outcomes were associated with the longest period of intervention and the most intensive case management (Rhode Island), but further evaluation is needed, and funding for such programs is a real and consistent concern. When combined with the literature on previous and existing programs nationwide, the voices of these participants provide a good idea of what may be next for a successful pre-release program in Georgia. 1) Planning services should begin sooner before release—possibly at the time of admission to prison—and should provide a longer period of follow-up, in order to capitalize on the time available for intervention with this vulnerable population and to more effectively prevent recidivism. The addition of support staff for the Georgia PRPP may allow this to occur. 2) Provision or expansion of the community mentoring program proposed in Spaulding’s 2009 study and supported by participants in these interviews, providing for matching of mentors with mentees by family and ethnic background, may be an important way to improve health outcomes among this population while facing a dearth of funding. 3) Securing and advocating for additional funding for vocational, counseling, and medical support services available to the general prison population is crucial, in order to support opportunities for skills advancement and true corrections in life path among a historically deprived incarcerated population. A cost-effectiveness analysis by state officials is recommended in order to measure the true economic value of such programs—especially in contrast to the public burden of unchecked recidivism. 4) A change in the Georgia laws that severely restrict the civil rights of ex-felons—including the right to vote, to be considered for many job opportunities, to be admitted to certain professional schools, and to receive state or federal financial aid for secondary education—is essential if former inmates are to be realistically expected to succeed outside of prison.

Darbo tikslas: įvertinti kineziterapijos procedūrų eiliškumo įtaką peties sąnario funkcijoms po artroskopinės sąauginio kapsulito operacijos. Darbo uždaviniai yra šie: 1. Įvertinti kineziterapijos įtaką pacientų po peties sąauginio kapsulito artroskopinės operacijos peties sąnario paslankumui ir jėgai priklausomai nuo kineziterapijos procedūrų eiliškumo. 2. Įvertinti kineziterapijos įtaką pacientų po peties sąauginio kapsulito artroskopinės operacijos skausmo intensyvumui ir savarankiškumui kasdieniniame gyvenime priklausomai nuo kineziterapijos procedūrų eiliškumo. 3. Paruošti rekomendacijas individualios kineziterapijos programos tobulinimui pacientams po peties sąauginio kapsulito artroskopinės operacijos. Hipotezė: ligonių po peties sąauginio kapsulito artroskopinės operacijos peties sąnario paslankumo, jėgos, skausmo ir savarankiškumo kasdieniniame gyvenime pokyčiai yra didesni kineziterapijos procedūras vykdant tokia seka: kineziterapija sausumoje atliekama po kineziterapijos vandenyje. Tyrimo metodika. Tyrimo kontingentą sudarė 36 tiriamieji, kurie buvo reabilituojami Palangos reabilitacijos ligoninėje 2005-2007 metais, po artroskopinės peties sąauginio kapsulito operacijos. Visiems pacientams taikyta ta pati reabilitacijos ir kineziterapijos programa, tik skyrėsi kineziterapijos procedūrų eiliškumas. Tiriamieji buvo suskirstyti į dvi grupes po 18 žmonių: I grupė – tiriamoji, kuriai kineziterapija sausumoje atliekama po kineziterapijos vandenyje, II grupė –... [toliau žr. visą tekstą] / The aim of this work: to evaluate the influence of the order of priority in physiotherapy procedures on treating adhesive shoulder function after arthroscopical release. The goals of this work are: 1. To estimate efficiency of physical therapy impact of shoulder mobility and strength subject to succession after arthroscopic operation of capsule adhesion; 2. To estimate of physical therapy impact of shoulder pain intensity and self-independence in daily life subject to succession after arthroscopic operation of capsule adhesion; 3. To prepare recommendation for individual physical therapy to accomplish program subject to succession after arthroscopic operation of capsule adhesion. Hypothesis: Shoulder mobility, strength, pain and self-independence alteration depends on physical therapy subject to succession after arthroscopic operation of shoulder capsule adhesion. Methodology of investigation: contingent of investigation consist of 36 patients after arthroscopic operation of shoulder capsule adhesion in Palanga rehabilitation hospital in 2005-2007. Each patient had the rehabilitation and physical therapy program. All investigative groups were divided in to groups of 18 patients. The first investigative group had overland physical therapy after physical therapy in swimming pool and the second control group had physical therapy in swimming pool after overland physical therapy. Analyzes of statistics was made with “SPSS” program and MS Excel. Conclusion. Established... [to full text]