Η επίδραση της συστηματικής λήψης κορτικοστεροειδών στην ενδοφθάλμια πίεση είναι επαρκώς τεκμηριωμένη και εξαρτάται από σημαντικό αριθμό παραγόντων. Αντίθετα, ελάχιστες και αντικρουόμενες πληροφορίες υπάρχουν για την επίδραση των ρινικών κορτικοστεροειδών στην ενδοφθάλμια πίεση. Σκοπός της μελέτης ήταν η διερεύνηση της επίδρασης του ρινικού κορτικοστεροειδούς fluticasone υπό μορφή ρινικών ψεκασμών στην ενδοφθάλμια πίεση σε ασθενείς που έπασχαν από αλλεργική ρινίτιδα. Η ενδοφθάλμια πίεση μετρήθηκε πριν και κάθε πέντε ημέρες από τη χορήγηση του φαρμάκου. Η στατιστική ανάλυση δεν αποκάλυψε σημαντικές διαφορές, γεγονός που φανερώνει ότι το συγκεκριμένο κορτικοστεροειδές δεν επηρέασε την ενδοφθάλμια. / The effect of systemic administation on intraocular pressure is well established. However less attention has been paid to the effect of steroids when administered in a nasal spray. We conducted a study to investigate a possible association between nasal steroids and elevated IOP in 54 patients who were being treated for allergic rinitis. IOP was measured before the patients started therapy and thereafter every five days during that therapy. Follow up ranged from 27 to 35 days. Statistical analysis revealed no significant elavation in IOP after nasal steroid administration.

This study developed an informative model of a nasal cavity of a Neanderthal and Anatomically Modern Human (AMH) hybrid based on the morphological measurements and nonmetric features of nonhuman primate hybrids. This study examined morphometric measurements and nonmetric traits of the interior nasal cavity of two species of baboons (olive and yellow) and their first generation hybrids to determine how hybridization affects the internal anatomy of the nasal cavity. The nasal cavity was chosen because the nasal cavities of Neanderthals and AMH are recognized as uniquely different in size and shape. This study found that functionally different regions within the baboon nasal cavity are altered in size and shape in response to hybridization. Changes in size and shape due to hybridization occurred in three regions, at the rhinion, choana, and mid-nasopharynx. In regions of more complex physiological function, the mid-bony cavity and the posterior nasopharynx, no size or shape response was observed, except a wider lateral recess. Males and females responded differently to hybridization; males showed heterosis and females showed heterosis in most areas, though dysgenesis in the inferior meatus. The opposing male and female trends may contribute to the greater sexual dimorphism observed in hybrids compared to parental taxa. This study found that frequencies of nonmetric traits in the baboon hybrid nasal cavity were no different from frequencies in parental taxa, nor were regional frequency differences observed because anterior and posterior nonmetric traits occurred at the same frequency. However, males expressed a significantly higher frequency of nonmetric traits than females. Assuming Neanderthal and AMH hybrid nasal cavities follow the trends observed in the baboon hybrid model, the Neanderthal and AMH hybrid nasal cavity would have a different shape and larger size at the rhinion, choana, and mid-nasopharynx, while the mid-bony cavity and posterior nasopharynx remained unchanged compared to parental taxa. However, because Neanderthals and AMH have been diverged for a longer time period, the traits of the nasal cavity may be very different in parental taxa due to adaptations to local conditions, which may result in hybrids with traits from one parent or the other. Further, an analysis of different hybridization scenarios between Neanderthals and AMH, based on observed hybridization in baboons and paleoanthropological evidence, suggests rapid gene swamping of the Neanderthal population by AMH during hybridization, as other authors have also concluded.

Since its initial discovery in 1922 by Banting and Best, the formulation of an oral insulin delivery system has ever been so troublesome. Unfortunately, insulin is indispensable in the treatment of diabetes mellitus, which affects approximately 350 million people worldwide. Various factors contribute to the peptide being such a persistently difficult hormone to be used in an oral formulation. The gastrointestinal tract is home to various protein digestive enzymes such as pepsins in the stomach and trypsin, chymotrypsin and carboxypeptidases in the small intestine, which digests insulin. Also the physical barrier of the gastrointestinal tract, i.e. the columnar epithelial layer which lines the tract, is a tightly bound collection of cells with minimal leakage and is thus a sound barrier for the absorption of peptides and hormones. The aim of this study is to determine whether a dosage form for insulin, entrapped in Pheroid™ vesicles and -micro sponges, can overcome these barriers and successfully deliver insulin at the site of action resulting in a significant therapeutic response. Initial phases of the study consisted of the manufacturing of Pheroid™ vesicles and - microsponges, entrapment of flourescein-isothiocyanate labelled insulin (FITC-insulin) into the Pheroid™. The Pheroid™-insulin complex was analysed with confocal laser scanning microscopy (CLSC) to determine drug loading. In vivo experiment in Sprague - Dawley rats were done where blood glucose levels as well as insulin blood levels were monitored after administration of different Pheroid insulin formulations. Firstly a standard reference was set by subcutaneous injection of insulin (0.5 IU/kg) in rats followed by a comparative study where administration to the stomach, colon and ileum (50.0 IUlkg insulin) were compared by means of blood insulin levels and therapeutic effect between the control and Pheroid™ complexes (Pheroid™ vesicles and microsponges). Each study was done by means of direct injection into the stomach, ileum or colon through which the insulin in saline (control) or insulin-Pheroid™ complex was administered. Nasal administration of 8.0 and 12.0 IU/kg insulin in saline (control) or insulin-Pheroid™ complex was done in the right nostril of Sprague - Dawley rats. Blood samples were taken from the artery carotis communis by means of an inserted cannula. Blood samples were taken just before administration and then at 5, 10, 15, 30, 60, 120 and 180 minutes after administration. Blood glucose levels were measured just after every blood sample was taken and plasma insulin levels were determined with a human insulin specific radioimmunoassay. The results were compared to the reference as well as the control to determine relative bioavailability. Through the results obtained it was discovered that in comparison with the various parts of the or tract, the ileum showed undoubtedly to be the best area of absorption where Pheroid™ vesicles revealed a peak 42.0 % lowering in blood glucose levels after 60 minutes and a peak plasma concentration of 244.0 /uID/ml after 5 minutes together with an 18.7 % lowering in blood glucose levels after just 5 minutes. After nasal administration of Pheroid™ microsponges (8.0 ID/kg insulin) a remarkable lowered blood glucose level of 19.2 % after 10 minutes and 36.5 % after 30 minutes as well as a peak plasma insulin level of220.2 /lID/ml after 3 hours was observed. Insulin entrapped in Pheroid™ microsponges administered at 12.0 ID/kg showed a maximum blood glucose lowering effect of72.4 % after 3 hours with a peak plasma level of 154.8 uID/ml also after 3 hours, thus showing a long acting effect. In conclusion, the delivery system based on Pheroid™ technology shows a sufficient therapeutic effect for insulin and is therefore promising for further in vivo evaluation and ultimately for medicinal use to patients suffering from diabetes mellitus. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

Since its initial discovery in 1922 by Banting and Best, the formulation of an oral insulin delivery system has ever been so troublesome. Unfortunately, insulin is indispensable in the treatment of diabetes mellitus, which affects approximately 350 million people worldwide. Various factors contribute to the peptide being such a persistently difficult hormone to be used in an oral formulation. The gastrointestinal tract is home to various protein digestive enzymes such as pepsins in the stomach and trypsin, chymotrypsin and carboxypeptidases in the small intestine, which digests insulin. Also the physical barrier of the gastrointestinal tract, i.e. the columnar epithelial layer which lines the tract, is a tightly bound collection of cells with minimal leakage and is thus a sound barrier for the absorption of peptides and hormones. The aim of this study is to determine whether a dosage form for insulin, entrapped in Pheroid™ vesicles and -micro sponges, can overcome these barriers and successfully deliver insulin at the site of action resulting in a significant therapeutic response. Initial phases of the study consisted of the manufacturing of Pheroid™ vesicles and - microsponges, entrapment of flourescein-isothiocyanate labelled insulin (FITC-insulin) into the Pheroid™. The Pheroid™-insulin complex was analysed with confocal laser scanning microscopy (CLSC) to determine drug loading. In vivo experiment in Sprague - Dawley rats were done where blood glucose levels as well as insulin blood levels were monitored after administration of different Pheroid insulin formulations. Firstly a standard reference was set by subcutaneous injection of insulin (0.5 IU/kg) in rats followed by a comparative study where administration to the stomach, colon and ileum (50.0 IUlkg insulin) were compared by means of blood insulin levels and therapeutic effect between the control and Pheroid™ complexes (Pheroid™ vesicles and microsponges). Each study was done by means of direct injection into the stomach, ileum or colon through which the insulin in saline (control) or insulin-Pheroid™ complex was administered. Nasal administration of 8.0 and 12.0 IU/kg insulin in saline (control) or insulin-Pheroid™ complex was done in the right nostril of Sprague - Dawley rats. Blood samples were taken from the artery carotis communis by means of an inserted cannula. Blood samples were taken just before administration and then at 5, 10, 15, 30, 60, 120 and 180 minutes after administration. Blood glucose levels were measured just after every blood sample was taken and plasma insulin levels were determined with a human insulin specific radioimmunoassay. The results were compared to the reference as well as the control to determine relative bioavailability. Through the results obtained it was discovered that in comparison with the various parts of the or tract, the ileum showed undoubtedly to be the best area of absorption where Pheroid™ vesicles revealed a peak 42.0 % lowering in blood glucose levels after 60 minutes and a peak plasma concentration of 244.0 /uID/ml after 5 minutes together with an 18.7 % lowering in blood glucose levels after just 5 minutes. After nasal administration of Pheroid™ microsponges (8.0 ID/kg insulin) a remarkable lowered blood glucose level of 19.2 % after 10 minutes and 36.5 % after 30 minutes as well as a peak plasma insulin level of220.2 /lID/ml after 3 hours was observed. Insulin entrapped in Pheroid™ microsponges administered at 12.0 ID/kg showed a maximum blood glucose lowering effect of72.4 % after 3 hours with a peak plasma level of 154.8 uID/ml also after 3 hours, thus showing a long acting effect. In conclusion, the delivery system based on Pheroid™ technology shows a sufficient therapeutic effect for insulin and is therefore promising for further in vivo evaluation and ultimately for medicinal use to patients suffering from diabetes mellitus. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

Transplants of olfactory ensheathing cells (OECs) from olfactory bulbs have recently been shown to support regrowth and reinnervation of damaged spinal cord, which has led to improved functional recovery. Using complete transection in adult rat, the studies presented in this thesis examine the role of peripherally derived olfactory tissue in promoting axonal regeneration and functional recovery. Chapter One and Two provide the background to the area of spinal cord regeneration and the methods used in this thesis. Chapter Three shows that transplants of OECs from rat olfactory lamina propria (OLP) are able to support axon regrowth in the lesioned spinal cord. The BBB score was significantly higher in experimental rats (5.4???0.84) compared with control animals (1.9???0.33) (P&lt0.001). These dissociated OECs from OLP can promote axonal regrowth through the lesion. Histological assessment showed that: 1) axons labelled with Fluororuby grew into the injury site in OECs-transplanted rats, with occasional fibres extending into the rostral cord; 2) brainstem neurons in the raphe nucleus were retrogradely labeled with Fluororuby; and 3) serotonergic axons were detectable distal to the lesion in OECs-transplanted rats. No fibres grew into the injured region and no retrograde labeling or serotonergic fibres were seen in control animals. The role of regenerated serotonergic fibres in OECs-transplanted rats is discussed. Chapter Four demonstrates that solid pieces of OLP dissected from the nose can re-establish the continuity of the transected cord and supply the OECs that can migrate to the cord stumps to support the axon regeneration. Experimental rats which received OLP from olfactory mucosa showed significantly greater locomotive recovery (BBB scores: OLP, 5.0???1.9; control, 1.5???0.5, p&lt0.0001). In animals with OLP transplants, histological analysis indicated that nerve fibres, expressing neurofilament and serotonin were present at the transection site. Locomotive recovery of the hindlimbs occurred, similar to that seen after OECs transplantation. Retrograde labeling of medullary raphe neurons and gigantocellular reticular nucleus occurred following Fluororuby injection in the cord distal to the lesion, further supporting the supraspinal origin of the 5-HT innervation in the present studies. These results indicate that OLP is effective in promoting partial spinal cord repair. Chapter Five examines functional recovery of spinal reflex circuitry, ie., H-reflex excitability using paired stimuli, in OLP-transplanted rats compared with normal and respiratory lamina propria (RLP) transplanted animals. H-reflex amplitude of the conditioned response was significantly reduced in OLP transplanted rats compared to RLP transplanted animals (p&lt 0.05). Therefore, hindlimb reflex excitability can be modulated by OLP transplants after transection of the spinal cord in adult rats. Chapter Six examines whether functional recovery can occur if transplantation of OLP tissue is delayed by 1 month after the spinal cord transection. The BBB score was significantly higher in experimental rats (4.3???0.8 for OLP) compared with control animals (1.0???0.3, P&lt 0.001), but recovery was less than after acute transplantation. Asx before, histological assessment of OLP animals showed: a) serotonergic axons were present in the cord below the transection site; b) brainstem raphe nuclei was retrogradely labeled; c) bisbenzimide pre-labeled cells from OLP transplants migrated in host spinal cord. These changes were not seen in control animals. These results indicate that OLP has the ability to promote axonal regeneration in chronically injured cord of adult rats. Chapter Seven compares the results from these three types of intervention. In conclusion, these studies show that peripherally derived OECs or solid pieces of OLP can promote partial spinal cord repair in acute or chronic transection injuries. Such tissue might provide a potential source for autologous grafting in human paraplegia.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Dissertation (Ph.D.)--Auburn University, 2006. / Abstract. Vita. Includes bibliographic references (p.120-127).

Thesis (M.S.)--University of Michigan, 1986.

Thesis (M.S.)--University of Michigan, 1986.