Background: The use of pure oxygen during preoxygenation and induction of general anaesthesia is a major cause of atelectasis. The interaction between reduced lung volume, resulting in airway closure, and varying inspiratory fractions of oxygen (FIO2) in determining the risk of developing atelectasis is still obscure. Methods: In this thesis, computed tomography (in studies I and II during anaesthesia, in studies III and IV postoperatively) was used to investigate the area of atelectasis in relation to FIO2 and varying levels of continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP). Study I investigated the short-term influence of reducing FIO2 during preoxygenation and induction of general anaesthesia, and the time to hypoxia during apnoea. Study II focused on the long-term effect of an FIO2 of 0.8 for preoxygenation. Study III applied CPAP/PEEP with an FIO2 of 1.0 or 0.8 for pre- and postoxygenation until extubation. After extubation, CPAP with an FIO2 of 0.3 was applied before the end of mask ventilation. Study IV compared two groups given CPAP/PEEP during anaesthesia and an FIO2 of 1.0 or 0.3 during postoxygenation, but without CPAP after extubation. Results: Study I showed a reduction in atelectasis with an FIO2 of 0.8 or 0.6, compared with 1.0, but the time to hypoxia decreased. In study II, atelectasis evolved gradually after preoxygenation. In study III, atelectasis was reduced with an FIO2 of 1.0 and CPAP/PEEP compared with an FIO2 of 1.0 without CPAP/PEEP. The intervention failed in the group given an FIO2 of 0.8, this group had more smokers. Atelectasis and age were correlated. In study IV, no difference was found between the groups. Post hoc analysis showed that smoking and ASA class increased the risk for atelectasis. Conclusion, the effect of reducing FIO2 during preoxygenation to prevent atelectasis might be short-lived. A lower FIO2 shortened the time to the appearance of hypoxia. Increasing lung volume by using CPAP/PEEP also decreased the risk of atelectasis, but the method might fail; for example in patients who are heavy smokers. In older patients care must be taken to reduce a high FIO2 before ending CPAP.

The five discrete, but related studies presented in this thesis investigate several aspects of the physiology and biochemistry of whole animals, perfused and isolated tissues from fishes and other vertebrates. Important fundamental questions about tissue metabolism and energy supply and utilisation in relation to oxygen supply, in addition to applied questions relating to commercial harvesting and post-mortem muscle physiology were addressed. Oxyconformance of oxygen consumption (VO2) at low oxygen delivery rates was shown using an isolated, perfused salmon tail preparation, composed primarily of skeletal muscle. Addition of pig red blood cells to the perfusing solution at a haematocrit of 5 or 10%, increasing the capacitance, resulted in oxyregulation of VO2 by the tail tissues. Below c.60 ml O2.kg-1.h-1 of oxygen delivery, VO2 was delivery dependent. Above this value additional oxygen delivery did not increase VO2 of resting muscle above c.35 ml O2 kg-1.h-1. The preparation was validated by measuring mitochondrial activity using MTT and blood flow distribution to the red and white muscle using fluorescent microspheres. Evidence of both O2-independence of VO2 in the vasculature and strict O2-dependence of VO2 in striated muscles of fishes and a mammal is presented using isolated vascular tissue and an in vitro tissue slice model. VO2 by vessels from rat, salmon and hagfish showed varying degrees of independence between PO2s of 15-95 mmHg in vitro (1 mmHg = 0.133 kPa). Above and below these values, VO2 was highly PO2-dependent. VO2 by cardiac and skeletal muscles from rat, salmon, snapper and hagfish were shown to relate linearly to PO2 between zero and 125 mmHg. VO2 in these tissues was highly dependent on tissue type (cardiac, red and white muscle) which correlated with haem protein concentration. The increase in VO2 in muscle slice mitochondria uncoupled with FCCP and DNP ruled out diffusion-limitation as a constraint on VO2. Mitochondrial activity was constant over time and reoxygenation of the Ringer bathing the tissues after the initial run down in PO2 resulted in VO2 rates that were unchanged from the starting values, demonstrating that the tissues remained viable over time. ATP turnover in red muscle was significantly increased at 100 mmHg relative to 30 mmHg, and increased in both treatments from values at the start. Our data suggest that ATP supply and ATP demand were reduced in conjunction with falling PO2. The effects of hydrogen sulphide (H2S) (derived from Na2S) and isoeugenol exposure on activity, VO2 and ventilation frequency (Vf) in a teleost fish are reported. In the H2S treatment group (200 μM Na2S) both resting VO2 and Vf decreased after 30 minutes of exposure, concurrent with narcosis and a loss of equilibrium. These events corresponded with a significant fall in VO2 (33%) and Vf (20%) by 15 minutes, both declining further to a nadir of 40% of resting values at 30 minutes. After flushing, VO2 increased to resting levels, with Vf remaining significantly depressed until 30 minutes of recovery. Recovery was accompanied by regained mobility and equilibrium and significantly increased VO2 and Vf. Isoeugenol anaesthetised fish (0.011 g.L-1) reached stage 4-5 of anaesthesia accompanied by significant decreases in VO2 (45%) and Vf (25%) at 25 minutes, both parameters declining further to around 64% and 38% respectively by 35 minutes. Similar to H2S exposed fish, VO2 increased to resting values after flushing, followed by a significant rise in VO2. Likewise, Vf had risen to resting values post-flushing, subsequently increasing significantly during recovery. Overall, VO2 in relation to resting rate was reduced in the isoeugenol treated animals, while in H2S treated fish, exposure there was increased oxygen usage, possibly associated with a toxic effect. H2S significantly reduced cytochrome c oxidase activity in muscle and gill tissue in vitro between 69-79% at 20 μM and 77-97% at 200 μM Na2S, while isoeugenol had no effect on activity in any tissue. Calorimetric and biochemical profiles of anoxic, post-mortem white muscle from Chinook salmon subjected to rested and exhausted harvesting regimens at their acclimation temperature (10°C) are reported. Prior to harvest rested animals were anaesthetised with 0.012 g.L-1 isoeugenol without disturbance. The muscle of these animals had a high metabolic rate at the time of death, at around 400 μW.g-1, which declined rapidly over the first 12 hours to15 μW.g-1. Exhausted animals were forced to swim and were crowded before capture, resulting in an initial heat output of <10 μW.g-1. Heat output was significantly greater in the rested group at the time of death and for 7 hours post-mortem. In both groups there was an exothermic event, occurring between 4 and 6 hours post-mortem amounting to a rise of around 35 μW.g-1. A one-phase exponential decay model appropriately described the net heat output of the rested profile minus the exhausted data. Rested animals had significantly higher initial cut surface pH (7.5 vs 6.7), tissue glycogen (16 vs 2 μmol.g-1), creatine phosphate (18 vs 0.1 μmol.g-1), ATP (6 vs 3.5 μmol.g-1) and potential energy (30 vs 7 μmol.g-1) than the exhausted group, which had significantly elevated tissue concentrations of lactate (43 vs 18 μmol.g-1) and glucose (5 vs 2 μmol.g-1). Potential energy in the form of ATP, glycogen and creatine phosphate remained elevated for an extended period post-mortem in rested animals while catabolites further down the chain such as inosine, hypoxanthine and uric acid accumulated at similar rates in both groups. We examined the relationship between exogenous and endogenous H2S and oxygen partial pressure in isolated hagfish and lamprey vessels that exhibit profound hypoxic vasoconstriction (HVC). In myography studies, H2S (Na2S) dose-dependently constricted dorsal aortas (DA) and efferent branchial arteries but did not affect ventral aortas or afferent branchial arteries, which was similar to the effects produced by hypoxia. Sensitivity of H2S-mediated contraction in hagfish and lamprey DA was enhanced by hypoxia. HVC in hagfish DA was enhanced by the H2S precursor cysteine and inhibited by amino-oxyacetate (AOA), an inhibitor of the H2S-synthesising enzyme, cystathionine β-synthase, and unaffected by propargyl glycine, an inhibitor of cystathionine λ-lyase. Oxygen consumption (MO2) of hagfish DA was constant between a PO2 of 15 and 115•mmHg, decreased when PO2 <15•mmHg, and increased if PO2 exceeded 115•mmHg. 10 μmol.l-1 H2S increased and concentrations above 100 μmol.l-1 H2S decreased MO2. Consistent with the effects on HVC, cysteine increased and AOA and hydroxylamine, an inhibitor of pyridoxyl 5’-phosphate-dependent enzymes, decreased MO2. These data show that H2S is a monophasic vasoconstrictor of specific cyclostome vessels and because hagfish lack vascular NO, and vascular sensitivity to H2S was enhanced at low PO2, it is unlikely that H2S contractions are mediated by either an H2S-NO interaction or an oxidation product of H2S. These experiments provide additional support for the hypothesis that the metabolism of H2S is involved in oxygen sensing/signal transduction in vertebrate vascular smooth muscle. Together the findings of this thesis contribute to the understanding of oxygen utilisation and energetics in relation to oxygen supply in a number of tissues. These data further our understanding of respiratory physiology and may have practical applications in the seafood industry.

Ovarian steroid hormones are known to produce several different effects in the brain. In addition to their role in gonadotropin release, ovulation and sexual behaviour they also seem to affect mood and emotions, as shown in women with the premenstrual tension syndrome. Some steroids have the ability to affect brain excitability. Estradiol decreases the electroshock threshold while progesterone acts as an anti-convulsant and anaesthetic in both animals and humans. Several earlier studies have shown a specific uptake of several steroids in the animal brain but only a few recent studies have established the presence of steroids in the human brain. In the present studies, the dissections of rat and human brains were carried out macroscopically and areas that are considered to be related to steroid effects were chosen. Steroid concentrations were measured by radioimmunoassay after extraction and separation with celite chromatography. The accuracy and specificity of these methods were estimated. In the animal studies, immature female rats were treated with Pregnant Mare's Serum Gonadotropin (PMSG) to induce simultaneous ovulations. Concentrations of estradiol and progesterone were measured in seven brain areas pre- and postovulatory. The highest concentration of estradiol, pre- and postovulatory, was found in the hypothalamus and differences between the two cycle phases were detected in most brain areas. The preovulatory concentrations of progesterone were low and the highest postovulatory concentration was found in the cerebral cortex. In one study, the rats were injected with pharmacological doses of progesterone to induce "anaesthesia". High uptake of progesterone was found and a regional variation in the formation of 5&lt;*-pregnane-3,20-dione in the brain with the highest ratio in the medulla oblongata. Concentrations of progesterone, 5a-pregnane-3*20-dione, estradiol and testosterone were determined in 17 brain areas of fertile compared to postmenopausal women. All steroids displayed regional differences in brain concentrations. Higher concentrations of estradiol and progesterone were found in the fertile compared to the postmenopausal women. In summary, these studies show that the concentrations of ovarian steroids in the brain are different at different endocrine states in both rats and humans and that there are regional differences in brain steroid distribution. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1987, härtill 5 uppsastser</p> / digitalisering@umu

Local anaesthetics are used regularly in the medical world for a variety of different procedures. Topical anaesthetics are used largely in minor skin breaking procedures, laceration repair and minor surgical procedures such as laryngoscopy, oesophagoscopy or urethroscopy (Franchi et al., 2008:186e1). The topical means of application of a local anaesthetic is non-invasive and painless that results in a good patient acceptability profile (Little et al., 2008:102). An existing commercial topical anaesthetic product contains a eutectic mixture of the amide-type local anaesthetics lidocaine hydrochloride (HCl) and prilocaine hydrochloride (HCl). This commercial product takes up to an hour to produce an anaesthetic effect. This is considered as a disadvantage in the use of topical anaesthetics, an hour waiting time is not always ideal in certain medical circumstances (Wahlgren & Quiding, 2000:584). This study compared the lag times, transdermal and topical delivery of lidocaine HCl and prilocaine HCl from four different semi-solid formulations with the inclusion of a current commercial product. One of the formulated semi-solid formulations included Pheroid™ technology, a novel skin-friendly delivery system developed by the Unit for Drug Research and Development at the North-West University, Potchefstroom Campus, South Africa. The skin is the body’s first line of defence against noxious external stimuli. It is considered the largest organ in the body with an intensive and complex structure. It consists of five layers with the first outer layer, the stratum corneum, the most impermeable (Williams, 2003:1). The stratum corneum has excellent barrier function characteristics and is the cause for the time delay in the transdermal delivery of active pharmaceutical ingredients (API) (Barry, 2007:569). Local anaesthetics need to penetrate all the epidermal skin layers in order to reach their target site, the dermis. Skin appendages as well as blood vessels and skin nerve endings are located in the dermis. Local anaesthetics have to reach the free nerve endings in the dermis in order to cause a reversible block on these nerves for a local anaesthetic effect (Richards & McConachie, 1995:41). Penetration enhancement strategies for the transdermal delivery of lidocaine and prilocaine have been investigated and include methods like liposomal entrapment (Franz-Montan et al., 2010; Müller et al., 2004), micellisation (Scherlund et al., 2000), occlusive dressing (Astra Zeneca, 2006), heating techniques (Masud et al., 2010) and iontophoresis (Brounéus et al., 2000). The Pheroid™ delivery system has improved the transdermal delivery of several compounds with its enhanced entrapment capabilities. Pheroid™ consists mainly of unsaturated essential fatty-acids, non-harmful substances that are easily recognised by the body (Grobler et al., 2008:285). The morphology and size of Pheroid™ is easily manipulated because it is a submicron emulsion type formulation which provides it with a vast flexibility profile (Grobler et al., 2008:284). Vesicular entrapment was used to entrap lidocaine HCl and prilocaine HCl in the Pheroid™ and incorporated into an emulgel formulation. An emulgel without the inclusion of Pheroid™ was formulated for comparison with the Pheroid™ emulgel as well as with a hydrogel. Pheroid™ solution was prepared and compared to a phosphate buffer solution (PBS) without Pheroid™, both containing lidocaine HCl and prilocaine HCl as APIs. Franz cell type transdermal diffusion studies were performed on the four semi-solid formulations (emulgel, Pheroid™ emulgel, hydrogel and the commercial product) and two solutions (PBS and Pheroid™). The diffusion studies were performed over a 12 h period followed by the tape stripping of the skin after each diffusion study. Caucasian female abdominal skin was obtained with consent from the donors. The skin for the diffusion cells were prepared by using a Zimmer Dermatome®. PBS (pH 7.4) was prepared as the receptor phase of the diffusion studies. The receptor phase was extracted at certain pre-determined time intervals and analysed with high performance liquid chromatography (HPLC) to determine the amount of API that had traversed the skin. Stratum corneum-epidermis samples and epidermis-dermis samples were prepared and left over night at 4 °C and analysed the next day with HPLC. This was done to determine the amount of API that accumulated in the epidermis-dermis and the amount of API that were left on the outer skin layers (stratum corneum-epidermis). The results from the Franz cell diffusion studies indicated that the emulgel formulation without Pheroid™ shortened the lag time of lidocaine HCl and that the emulgel formulated with Pheroid™ shortened the lag time of prilocaine HCl, when compared to the commercial product. Pheroid™ did not enhance the flux of lidocaine HCl and prilocaine HCl into the skin. The hydrogel formulation demonstrated a high transdermal flux of prilocaine HCl due to the hydrating effect it had on the stratum corneum. The commercial product yielded high flux values for both APIs but it did not result in a high concentration of the APIs delivered to the epidermis-dermis. Pheroid™ technology did, however, enhance the epidermal-dermal delivery of lidocaine HCl and prilocaine HCl into the skin epidermis-dermis. The stability of the emulgel formulation, Pheroid™ emulgel formulation and the hydrogel formulation was examined over a 6 month period. The formulations were stored at 25 °C/60% RH, 30 °C/60% RH and 40 °C/75% RH. The API concentration, mass, pH, zeta potential, particle size, viscosity and visual appearance for each formulation at the different storage conditions were noted and compared at month 0, 1, 2, 3 and 6 to determine if the formulations remained stable for 6 months. The results obtained from the stability study demonstrated that none of the formulations were stable for 6 months. The emulgel remained stable for the first 3 months. At 6 months, large decreases in API concentration and pH occurred which could cause a loss of anaesthetic action in the formulations. The Pheroid™ emulgel formulation did not remain stable for 6 months. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Local anaesthetics are used regularly in the medical world for a variety of different procedures. Topical anaesthetics are used largely in minor skin breaking procedures, laceration repair and minor surgical procedures such as laryngoscopy, oesophagoscopy or urethroscopy (Franchi et al., 2008:186e1). The topical means of application of a local anaesthetic is non-invasive and painless that results in a good patient acceptability profile (Little et al., 2008:102). An existing commercial topical anaesthetic product contains a eutectic mixture of the amide-type local anaesthetics lidocaine hydrochloride (HCl) and prilocaine hydrochloride (HCl). This commercial product takes up to an hour to produce an anaesthetic effect. This is considered as a disadvantage in the use of topical anaesthetics, an hour waiting time is not always ideal in certain medical circumstances (Wahlgren & Quiding, 2000:584). This study compared the lag times, transdermal and topical delivery of lidocaine HCl and prilocaine HCl from four different semi-solid formulations with the inclusion of a current commercial product. One of the formulated semi-solid formulations included Pheroid™ technology, a novel skin-friendly delivery system developed by the Unit for Drug Research and Development at the North-West University, Potchefstroom Campus, South Africa. The skin is the body’s first line of defence against noxious external stimuli. It is considered the largest organ in the body with an intensive and complex structure. It consists of five layers with the first outer layer, the stratum corneum, the most impermeable (Williams, 2003:1). The stratum corneum has excellent barrier function characteristics and is the cause for the time delay in the transdermal delivery of active pharmaceutical ingredients (API) (Barry, 2007:569). Local anaesthetics need to penetrate all the epidermal skin layers in order to reach their target site, the dermis. Skin appendages as well as blood vessels and skin nerve endings are located in the dermis. Local anaesthetics have to reach the free nerve endings in the dermis in order to cause a reversible block on these nerves for a local anaesthetic effect (Richards & McConachie, 1995:41). Penetration enhancement strategies for the transdermal delivery of lidocaine and prilocaine have been investigated and include methods like liposomal entrapment (Franz-Montan et al., 2010; Müller et al., 2004), micellisation (Scherlund et al., 2000), occlusive dressing (Astra Zeneca, 2006), heating techniques (Masud et al., 2010) and iontophoresis (Brounéus et al., 2000). The Pheroid™ delivery system has improved the transdermal delivery of several compounds with its enhanced entrapment capabilities. Pheroid™ consists mainly of unsaturated essential fatty-acids, non-harmful substances that are easily recognised by the body (Grobler et al., 2008:285). The morphology and size of Pheroid™ is easily manipulated because it is a submicron emulsion type formulation which provides it with a vast flexibility profile (Grobler et al., 2008:284). Vesicular entrapment was used to entrap lidocaine HCl and prilocaine HCl in the Pheroid™ and incorporated into an emulgel formulation. An emulgel without the inclusion of Pheroid™ was formulated for comparison with the Pheroid™ emulgel as well as with a hydrogel. Pheroid™ solution was prepared and compared to a phosphate buffer solution (PBS) without Pheroid™, both containing lidocaine HCl and prilocaine HCl as APIs. Franz cell type transdermal diffusion studies were performed on the four semi-solid formulations (emulgel, Pheroid™ emulgel, hydrogel and the commercial product) and two solutions (PBS and Pheroid™). The diffusion studies were performed over a 12 h period followed by the tape stripping of the skin after each diffusion study. Caucasian female abdominal skin was obtained with consent from the donors. The skin for the diffusion cells were prepared by using a Zimmer Dermatome®. PBS (pH 7.4) was prepared as the receptor phase of the diffusion studies. The receptor phase was extracted at certain pre-determined time intervals and analysed with high performance liquid chromatography (HPLC) to determine the amount of API that had traversed the skin. Stratum corneum-epidermis samples and epidermis-dermis samples were prepared and left over night at 4 °C and analysed the next day with HPLC. This was done to determine the amount of API that accumulated in the epidermis-dermis and the amount of API that were left on the outer skin layers (stratum corneum-epidermis). The results from the Franz cell diffusion studies indicated that the emulgel formulation without Pheroid™ shortened the lag time of lidocaine HCl and that the emulgel formulated with Pheroid™ shortened the lag time of prilocaine HCl, when compared to the commercial product. Pheroid™ did not enhance the flux of lidocaine HCl and prilocaine HCl into the skin. The hydrogel formulation demonstrated a high transdermal flux of prilocaine HCl due to the hydrating effect it had on the stratum corneum. The commercial product yielded high flux values for both APIs but it did not result in a high concentration of the APIs delivered to the epidermis-dermis. Pheroid™ technology did, however, enhance the epidermal-dermal delivery of lidocaine HCl and prilocaine HCl into the skin epidermis-dermis. The stability of the emulgel formulation, Pheroid™ emulgel formulation and the hydrogel formulation was examined over a 6 month period. The formulations were stored at 25 °C/60% RH, 30 °C/60% RH and 40 °C/75% RH. The API concentration, mass, pH, zeta potential, particle size, viscosity and visual appearance for each formulation at the different storage conditions were noted and compared at month 0, 1, 2, 3 and 6 to determine if the formulations remained stable for 6 months. The results obtained from the stability study demonstrated that none of the formulations were stable for 6 months. The emulgel remained stable for the first 3 months. At 6 months, large decreases in API concentration and pH occurred which could cause a loss of anaesthetic action in the formulations. The Pheroid™ emulgel formulation did not remain stable for 6 months. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Cerebral blood flow dynamics is an essential component for preserving cerebral integrity. Cerebral blood flow abnormalities are often seen in patients with central nervous system pathologies such as epilepsy, migraine, Alzheimer's Disease, vascular dementia, stroke, and even HIV/AIDS. There is increasing clinical and experimental evidence implicating cerebral hypoperfusion during ageing. The determination of cerebral perfusion has therefore become an important objective in physiological, pathological, pharmacological, and clinical investigations. The knowledge of regional cerebral blood flow further provides useful diagnostic information and/or data for a better understanding of the complex clinical presentations in patients with neurological and psychiatric disorders. Several cerebrovasoactive drugs have found application in the clinical setting of cerebrovascular diseases such as migraine and dementia. Due to the similarities between humans and non-human primates with respect to their brains, both structurally and behaviourally, numerous studies have been conducted and several non-human primate models have been developed for physiological, pathological, pharmacological, and clinical studies, amongst others in Parkinson's disease and diabetes. The relatively large size of the Cape baboon Papio Ursinus with a weight of 27-30 kg for a large male, makes this primate especially suitable for in vivo brain studies using radiotracers and Single Photon Emission Computed Tomography (SPECT). The main aim of the current study was therefore to develop a suitable radiotracer (99m Tc-hexamethylpropylene amine oxime (HMPAO) or 99m Tc_ethyl_cysteinatedimer (ECD) or 123l-iodoamphetamine (IMP)) for adapted in vivo cerebral blood flow measurements in a non-human primate (Papio ursinus) as an investigative model. The model was to be validated and applied in various drug studies for the evaluation of pharmacological interventions. The study design made use of split-dose methodology, whereby the radiopharmaceutical (radiotracer) was administered twice during each study. The first administration was injected soon after the induction of the anaesthesia, and was followed by the first SPECT data acquisition. The second administration of the radioligand, a double dose of radioactivity with respect to the first radioligand injection, was done at a specific time during the study, which took into account the pharmacodynamics of the drug. A second SPECT data acquisition followed subsequently. The drugs that were included in the study were acetazolamide, a carbonic acid anhydrase inhibitor (often used in nuclear medicine to determine cerebral reserve); sumaptriptan, a 5-HT (serotonin) agonist used for treatment of migraine; sodium valproate (an anti-epileptic drug); nimodipine, a calcium channel blocker and nitro-glycerine, a vasodilator used for angina. Arterial blood pressures were recorded from a catheter in the femoral artery and heart rates were concurrently monitored. The split-dose method was successfully applied to develop a non-human primate cerebral blood flow model under anaesthesia. The model showed differences in cerebral perfusion of the different anaesthesia regimes. These anaesthesia data sets were suitable as control/baseline results for drug intervention studies. Acetazolamide evaluation through the split-dose method in the baboon confirmed the sensitivity of the model by presenting comparable perfusion. This result compared to those already familiar prompted the model to be applied in pharmacological intervention studies. Subsequent results of these investigations showed increases in perfusion for single drug nimodipine treatment (25%). However, nimodipine attenuated the increases in perfusion when administered in combination with acetazolamide. Sumatriptan was able to decrease and normalise the increased perfusion after long duration anaesthesia. Decreased cerebral blood flow was observed for combinations of nimodipine with sodium valproate suggesting drug-drug interaction with important clinical implications. Similar decreases were found also for sumatriptan and nitro-glycerine when administered in combination with nimodipine. Studies with the various tracers (99m Tc_HMPAO or 99m Tc_ECD or 123l_IMP) showed clear differences in the perfusion data, confirming variation in the biochemical performance of the tracers. These differences, if not taken into consideration, caution for inappropriate clinical conclusions and subsequent erroneous therapeutic decisions. Improvement of radiotracer efficacy was subsequently attempted through application of the cyclodextrine complexation approach. Although cyciodextrine technology did not markedly improve the brain disposition of the 99m Tc-ECD, protection of the tracer against degradation was demonstrated. This study encouraged further exploration of this method for protection of the tracer against chemical and metabolic degradation. The current study was aimed to develop and effectively apply a non-human primate model with nuclear medicine technology for cerebral blood flow determinations after pharmacological interventions. This was achieved through the split-dose method and dedicated computer programming, which yielded a successful model with the non-human primate under anaesthesia. The model was validated with the application of acetazolamide to confirm familiar cerebrovascular reserve results, indicating that the model is sensitive to CBF changes. The model was also effectively applied in several pharmacological intervention studies, whereby cerebropharmacodynamics of selected drugs were investigated and established. This unique model of a non-human primate, Papio ursinus for cerebral blood flow determinations has served pharmacological research successfully during the past 12 years and could do so in the future, with scope to investigate new frontiers with improved technologies. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2004.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2008. / Härtill 5 uppsatser.

Made available in DSpace on 2016-12-08T16:24:20Z (GMT). No. of bitstreams: 1 PGCA15MA164.pdf: 3526630 bytes, checksum: f6dd4ad7f5a99171009a22e7f77d67e0 (MD5) Previous issue date: 2015-11-27 / The face of stress, agitation and respiratory distress chemical containment uncooperative animal is essential for the realization of an electro echocardiographic examination or appropriate. The objectives of the study in phase I were to evaluate the effects of different protocols of sedation on systemic blood pressure, echocardiographic and electrocardiographic parameters in dogs and in Phase II were to investigate the effects of different protocols of anesthesia on systemic blood pressure, echocardiographic and electrocardiographic parameters in dogs. In phase I (sedation), animals were sedated with acepromazine / butorphanol protocol (AB), acepromazine / methadone (AM), acepromazine / methadone / midazolam (MAM) and methadone (M). The statistical analysis was performed for parametric data by t test or ANOVA ONE WAY RM, and for nonparametric data, we used the Kruskal-Wallis Anova One Ranks and the Wilcoxon Signed Rank Test. In phase I, the reduction in SBP was observed in dogs of AB, MAM, AM groups, after sedation; group M there was no significant decrease in SBP. In electrocardiography not suggestive of arrhythmias or hypoxia in any of sedation protocols were observed. No changes were observed in the cardiac dimensions, assessed by echocardiography after sedation. Fractional shortening (FS) was reduced after sedation in the AM group; yet for this parameter, dogs sedated with AB showed less decrease of FS, differing from the other groups. Observed decrease in cardiac index (CI) in dogs of groups AM and M. The animals of group AB were less resistant to doing the tests, showing better sedation scores than other treatments. In phase II (induction), 24 male dogs were SRD were used, with an average weight of 12.40 ± 3.1 kg, which were randomly divided into 4 groups (n = 6). All animals were sedated with acepromazine protocol (0.05 mg / kg) / butorphanol (0.3 mg / kg) (AB). Fifteen minutes after anesthesia was induced with diazepam (0.5 mg / kg) / etomidate (1 mg / kg) (A), or diazepam (0.5 mg / kg) / ketamine (3 mg / kg) (CD) or propofol (4 mg / kg) (P) or ketamine (1 mg / kg) / propofol (3 mg / kg) (PC). PAS assessment, electrocardiography, and echocardiography was performed immediately before application of protocol sedation (baseline) and 15 minutes after sedation (M1) and immediately after induction of anesthesia (M2). In phase II, no significant differences were observed in SBP and hemodynamic variables such as cardiac index, fractional shortening, ejection fraction, assessed by echocardiography or changes of pace / myocardial hypoxia, evaluated by electrocardiogram between the different groups. SBP decreased after induction of anesthesia in groups DE and CP. Heart rate decreased significantly only in the CD group. It was concluded that the association acepromazine / butorphanol was the best protocol for sedation. All induction protocols evaluated similarly reduced SBP keeps stable manner and the IC in dogs pre-medicated None of induction protocols evaluated promotes significant echocardiographic changes and electro. The ketamine / diazepam decreased the myocardial relaxation / Diante do estresse, agitação e angústia respiratória a contenção química do animal não cooperativo é essencial para a realização dos exame eletro ou ecocardiográficos. Os objetivos do estudo, na fase I, foram avaliar os efeitos de diferentes protocolos de sedação e na fase II foram investigar as consequências de diferentes protocolos de indução anestésica, ambos sobre a pressão arterial sistêmica, parâmetros ecocardiográficos e eletrocardiográficos em cães. Na fase I (sedação), foram utilizados 24 cães, machos, SRD, com peso médio de 9,87±3,0kg, os quais foram alocados aleatoriamente em 4 grupos (n=6), submetidos a sedação com os protocolos acepromazina (0,05 mg/kg) / butorfanol (0,3 mg/kg) (AB), acepromazina (0,05mg/kg) / metadona (0,3mg/kg) (AM), acepromazina (0,03mg/kg) /metadona (0,3 mg/kg) / midazolam (0,3mg/kg) (MAM) e metadona (0,3 mg/kg) (M). A análise estatística foi realizada para os dados paramétricos através do teste T pareado ou ONE WAY RM ANOVA, e para os dados não paramétricos, utilizou-se o teste de Kruskal-Wallis e o teste de Wilcoxon Signed Rank Test. Na fase I, a PAS reduziu nos cães dos grupos AB, MAM, AM, após a sedação; no grupo M não houve queda significativa nos valores de PAS. Na eletrocardiografia observou-se redução significativa da FC após sedação em todos grupos estudados. Foi detectado bradicardia após sedação em 2 cães do grupo M e 1 animal do grupo AM. A duração da onda P aumentou após sedação nos grupos AM e M. Não foram observadas alterações nas dimensões cardíacas, avaliadas pela ecocardiografia, após sedação. A fração de encurtamento (FS) reduziu após sedação no grupo AM; os cães sedados com AB apresentaram menor queda da FS, diferindo dos demais grupos. Observou-se redução do índice cardíaco (IC) nos cães dos grupos AM e M. Os animais do grupo AB foram menos resistentes a execução dos exames, apresentando melhores escores de sedação do que os demais tratamentos. Na fase II (indução), foram utilizados 24 cães, machos, SRD, com peso médio de 12,40±3,1 kg, os quais foram alocados aleatoriamente em 4 grupos (n=6). Todos animais foram sedados com o protocolo acepromazina (0,05 mg/kg) / butorfanol (0,3 mg/kg) (AB). Após quinze minutos foi realizada indução anestésica com diazepam (0,5 mg/kg)/ etomidato (1 mg/kg) (DE), ou diazepam (0,5 mg/kg) / cetamina (3 mg/kg) (CD), ou propofol (4 mg/kg) (P) ou cetamina (1 mg/kg) / propofol (3 mg/kg) (CP). Foi realizada avaliação da PAS, eletrocardiografia e ecocardiografia imediatamente antes da aplicação do protocolo de sedação (basal) e 15 minutos após a sedação (M1) e imediatamente após a indução anestésica (M2). Na fase II, não foram observadas diferenças significativas na PAS e nas variáveis hemodinâmicas como índice cardíaco, fração de encurtamento, fração de ejeção, avaliadas através da ecocardiografia, nem alterações de ritmo/hipóxia do miocárdio, avaliadas pelo eletrocardiograma, entre os diferentes grupos. A PAS reduziu após indução anestésica nos grupos DE e CP. A frequência cardíaca reduziu significativamente somente no grupo CD. Concluiu-se que a associação acepromazina/butorfanol foi o melhor protocolo de sedação. Todos protocolos de indução avaliados reduzem de maneira semelhante a PAS e mantém estáveis o IC em cães pré medicados Nenhum dos protocolos de indução avaliados promove alterações eletro e ecocardiográficas significativas. A associação cetamina /diazepam promoveu redução no relaxamento miocárdico

Submitted by Leonardo de Freitas Guimarães Arcoverde Credie (leo_credie@yahoo.com.br) on 2018-05-14T22:08:59Z No. of bitstreams: 1 Tese completa.pdf: 11151658 bytes, checksum: de6b02496163d822cbea198d463ac878 (MD5) / Approved for entry into archive by Sulamita Selma C Colnago null (sulamita@btu.unesp.br) on 2018-05-15T14:14:48Z (GMT) No. of bitstreams: 1 credie_lfga_dr_bot.pdf: 11151658 bytes, checksum: de6b02496163d822cbea198d463ac878 (MD5) / Made available in DSpace on 2018-05-15T14:14:48Z (GMT). No. of bitstreams: 1 credie_lfga_dr_bot.pdf: 11151658 bytes, checksum: de6b02496163d822cbea198d463ac878 (MD5) Previous issue date: 2018-03-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Este estudo clínico prospectivo e aleatório objetivou descrever a sonoanatomia do espaço peridural lombossacral (LS) e avaliar e comparar a técnica guiada em tempo real com auxílio da ultrassonografia (US), em relação à palpação das referências anatômicas, para anestesia peridural em cães normais (escore de condição corporal – ECC ≤ 5) ou obesos (ECC ≥ 6). Para tal 72 animais provenientes de tutores, foram subdivididos igualmente em quatro grupos: PG1 e PG2 (Grupo Palpação 1 em animais normais e Grupo Palpação 2 em animais obesos, respectivamente), nos quais a técnica de anestesia peridural baseou-se nas referências anatômicas e perda de resistência à administração do fármaco e grupos USG1 e USG2 (Punção Guiada por US1 em animais normais e Punção Guiada por US2 em animais obesos, respectivamente), nos quais a técnica de anestesia peridural foi guiada exclusivamente pelo US. Para identificação das estruturas, utilizaram-se os cortes sagital, parassagital oblíquo e transversal. Aferiu-se a distância entre a pele e o ligamentum flavum (LF) nos grupos USG1 e USG2. Para confirmação exata da punção guiada por US, observaram-se a movimentação da agulha no momento da punção do LF e o fluxo de anestésico administrado, através da migração pelo canal peridural. Após a punção, confirmou-se a eficácia do bloqueio locorregional no período perioperatório. A utilização da ultrassonografia possibilitou a visualização das estruturas do espaço peridural LS, bem como o momento exato da punção e o fluxo do anestésico local nos espaços intervertebrais entre a 6ª (L6) e 7ª vértebras (L7), ou entre a 5a (L5) e 6a vértebras (L6) em todos os pacientes dos grupos USG1 e USG2, em ambos os cortes. As medidas entre pele e LF foram iguais nos cortes sagital e transversal, sendo 2,45 0,48 cm e 2,42 0,49 cm respectivamente para USG1 e 3,07 0,74 cm e 3,06 0,73 cm respectivamente para USG2. Nos grupos guiados por US, o número de contato entre agulha e tecido ósseo (USG1= 0,16 0,38 e USG2= 0,88 1,67) e refluxo de sangue na agulha (USG1= 5,5% e USG2= 0%) foram menores do que nos grupos guiados por palpação (contato agulha/osso: PG1= 0,88 1,67 e PG2= 2,72 2,02; refluxo de sangue: PG1= 11,1% e PG2= 22,2%). Concluiu-se que a anestesia peridural LS guiada por US possibilitou observar a sonoanatomia da região, acompanhar a introdução da agulha até o correto posicionamento no espaço peridural e visualizar a administração do anestésico local em tempo real, de forma independente de palpação de estruturas anatômicas, tanto em animais normais como em obesos, o que é uma vantagem ao se realizar anestesia peridural em animais com ECC ≥ 6. / This prospective and randomized clinical study aimed to describe the sonoanatomy of the lumbosacral epidural space and to evaluate and compare the real time guided ultrassonography (US) technique in comparison to palpation of anatomical references, to perform epidural anesthesia in normal (body condition score ≤ 5) or obese (body condition score ≥ 6). Seventy two client dogs were equally distributed in four groups, PG1 and PG2 (Palpation group 1 in normal animals and Palpation group 2 in obese animals, respectively), in which epidural anesthesia technique was based on palpation of anatomical references and loss of resistance to injection, and groups USG1 e USG2 (Ultrasound guided group 1 in normal animals and ultrasound guided group 2 in obese animals, respectively), in which the technique was guided only by US. Structures were identified in the sagittal, parasagittal oblique and transverse sections. The distance between skin and ligamentum flavum (LF) was measured in groups USG1 and USG2. Correct introduction and position of the needle in the epidural space and the flow of local anesthetic through the epidural canal was confirmed by US. The effectiveness of epidural anesthesia was confirmed in the perioperative period. With the use of US it was possible to define the sonoanatomy and to observe both the correct placement of the needle in the lumbosacral epidural space and the local anesthetic flowing between the sixth (L6) and seventh (L7) or fifth (L5) and sixth lumbar vertebrae in all dogs of the USG1 and USG2 groups, both in parasagittal oblique and in transversal approaches. The distances between skin and LF at the sagittal and transversal approaches were 2.45 0.48 cm and 2.42 0.49 cm respectively for USG1 and 3.07 0.74 cm and 3.06 0.73 cm respectively for USG2. The needle to bone contact events (USG1= 0.16 0.38 and USG2= 0.88 1.67) and presence of blood in the syringe (USG1= 5.5% e USG2= 0%) were lower than the palpation guided epidural anesthesia (needle to bone contacts: PG1= 0.88 1.67 and PG2= 2.72 2.02; blood in the syringe: PG1= 11.1% and PG2= 22.2%). The use of US provided accurate information about sonoanatomy of the LS epidural space in dogs, guided the positioning for the introduction of the needle without palpation of the anatomical structures, enabled to observe the correct injection of local anesthetic into the epidural space even in obese patients, and reduced the number of attempts to perform epidural anesthesia when compared to palpation of anatomical landmarks and loss of resistance technique. / 049/2015

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / O transporte de peixes vivos à um estÃmulo adverso à homeostase dos peixes. à uma prÃtica traumÃtica para os animais, pois envolve a captura, a manipulaÃÃo, o armazenamento dos indivÃduos e o deslocamento, atà a liberaÃÃo, o que sugere a necessidade de um procedimento para minimizar estes estressores. O objetivo deste trabalho foi avaliar o efeito do Ãleo de cravo nas respostas metabÃlicas e iÃnicas de juvenis de tilÃpia do Nilo, submetidos à simulaÃÃo do transporte em sacos plÃsticos, em diferentes densidades. Foram realizados dois experimentos: no primeiro foram avaliadas quatro concentraÃÃes de Ãleo de cravo (quatro repetiÃÃes, cada): 5, 10, 15 e 20 mg L-1, para examinar o comportamento dos peixes durante e apÃs a simulaÃÃo do transporte, a sobrevivÃncia e a qualidade da Ãgua. Foram utilizados vinte peixes por saco de transporte (50 g L-1); No segundo experimento, se utilizou apenas a melhor concentraÃÃo do anestÃsico, observado no primeiro experimento. Os peixes foram estocados em sacos plÃsticos nas densidades de 16, 28 e 40 peixes por saco, equivalente a 140, 245 e 350 g L-1, respectivamente. ApÃs nova simulaÃÃo de transporte, foram avaliados os nÃveis de glicose sanguÃnea, lactato, Ãons cloreto, magnÃsio e cÃlcio. No primeiro experimento, as duas menores concentraÃÃes foram ineficientes para anestesiar os animais. A concentraÃÃo de 20 mg L-1 amenizou a excreÃÃo de compostos nitrogenados, porÃm resultou num elevado Ãndice de mortalidade, enquanto a concentraÃÃo de 15 mg L-1 apresentou os resultados mais satisfatÃrios. No segundo experimento, o anestÃsico nÃo foi capaz de minimizar a elevaÃÃo dos nÃveis de glicose e lactato, independente da densidade utilizada. Quanto as variÃveis iÃnicas, com exceÃÃo do Mg+2, a utilizaÃÃo do Ãleo de cravo conseguiu manter os nÃveis dos Ãons Cl- e Ca+2. O uso do Ãleo de cravo apresentou pouco efeito preventivo ao estresse causado pela simulaÃÃo do transporte, podendo ter atuado inclusive como agente estressor adicional. / Transport of live fish is a harmful stimulus to organisms homeostasis. This practice is traumatic for the animals, because itâs involves the capture, handling and storage and the displacement of individuals, until the release. This suggests the need for a procedure to reduce these stressors. The objective of this study was to evaluate the effect of clove oil in ionic and metabolic responses of juvenile Nile tilapia, undergoing transport simulation in plastic bags, in different densities. Two experiments were conducted: the first evaluated four concentrations of clove oil (four replicates each): 5, 10, 15 and 20 mg L-1, to examine fishes behavior during and after the transport simulation, survival and water quality. Twenty fishes were used per carry bag (50 g L-1): In the second experiment, only the best anesthetic concentration observed in the first experiment was used. Fishes were stored in plastic bags at densities of 16, 28 and 40 fish per bag, equivalent to 140, 245 and 350 g L-1, respectively. After a new transport simulation, the levels of blood glucose, lactate, chloride ions, magnesium and calcium were evaluated. In the first experiment, the two lower concentrations were ineffective to anesthetize the animals. The concentration of 20 mg L-1 attenuated the excretion of nitrogenous compounds, but resulted in a high mortality rate, while the concentration of 15 mg L-1 showed the most satisfactory results. In the second experiment, the anesthetic was not able to minimize the increasing levels of glucose, lactate, independent of the density used. About the ionic variables, the use of clove oil was able to maintain levels of Cl-and Ca +2, except for Mg +2. The use of clove oil showed little preventive effect on stress caused by transport simulation, and may even have acted as an additional stressor agent.