Objectives: To explore the pain mechanism and the origin of the pain and to evaluate a short-term pain relief treatment in women suffering from CPP persisting after childbirth in order to enable physiotherapeutic intervention. Material and methods: Thirty-six parous women with chronic pelvic pain persisting after childbirth were recruited at the Department of Physiotherapy, SundsvallHospital and by advertisements in newspapers and 29 parous women without chronic pelvic pain were recruited from an organized gynaecological screening at a midwifery surgery. All women were provoked by intra-pelvic palpation of 13 predetermined intra-pelvic landmarks. The provoked pain distribution was expressed in pain drawings and the pain intensity verbally on a Likert scale.Also, in a randomised controlled trial the 36 women with chronic pelvic pain were allocated to bilateral injection treatment with either triamcinolone or saline solutions, given once on the ischial spine with follow-up after four weeks. Results: Referred pain provoked on intra-pelvic landmarks follows a specific pattern. In general, pain provoked by palpation of the posterior intra-pelvic landmarks was mostly referred to the sacral region and pain provoked by palpation of the ischial and pubic bones was mostly referred to the groin and pubic regions. In women with chronic pelvic pain the provoked pain distribution area and pain intensity were magnified as compared to women without chronic pelvic pain. In the clinical trial decreased pain intensity, decreased distribution of pain and improved physical function was achieved among the triamcinolone treatment group as compared to the saline treatment group. Also, a positive correlation was shown between reduced pain intensity and improved function. Conclusions: Referred pain patterns provoked on intra-pelvic landmarks in women with chronic pelvic pain persisting after childbirth are consistent with sclerotomal sensory innervations and indicates allodynia and central sensitisation. This suggests that pain mapping can be used to evaluate and confirm the pain experience and contribute to diagnosis. Also, the pain intensity provoked by stimulation of the intra-pelvic landmarks is suggested to be useful to differentiate women with chronic pelvic pain from those without. Corticosteroid treatment to the ischial spine resulted in decreased pain and increased function.

Posttraumatic stress disorder (PTSD) is a severe anxiety disorder characterised by hypothalamic-pituitary-adrenal (HPA)-axis abnormalities, hyperarousal, anxiety, flashbacks of trauma memories and avoidance. Increasing evidence is now accumulating that the disorder is also associated with shrinkage of the hippocampus and cognitive dysfunction that may have its origin in stress-induced excitotoxicity. Animal studies have indeed highlighted a potential role of the excitotoxic glutamatenitric oxide (NO) pathway in the stress response. Since PTSD appears to be an illness that progresses and worsens over time after an initial severe traumatic event, this study has used an animal model that emphasises repeated trauma to investigate the effect of stress on hippocampal NO synthase (NOS) activity, the release of the nitrogen oxide metabolites of NO (NOx), and also the evoked release of cGMP. Furthermore, the modulation and dependency of these responses on glutamate, NO and cGMP activity using drugs selective for these targets, will also be investigated. Rats (n=10/group) were exposed to repeated stress together with saline or drug administration immediately after the stress procedure and continuing for one week post-stress. The animals were then sacrificed for assay of hippocampal NOS activity, NO, and cGMP accumulation. Animals received either the glutamate-NMDA receptor antagonist, memantine (MEM;5mg/kg ip/d), the neuronal NOS selective inhibitor, 7- nitroindazole monosodium salt (7-NINA;20mg/kg ip/d), the cGMP-specific PDE inhibitor, sildenafil (SIL;10mg/kg ip/d) or the NFkb antagonist, pyrollidine dithiocarbamate (PDTC;70mg/kg ip/d). The latter inhibits the nuclear transcription factor, NFkb, responsible for inducing the expression of iNOS, while it also appears to mediate the glutamatergic actions on NOS expression, Stress significantly increased hippocampal NOS activity, as well as significantly increased hippocampal cGMP and NO, levels. These increases were blocked by pretreatment with either PDTC or 7-NINA, while memantine was without effect. Sildenafil significantly augmented stress induced NO, accumulation, as well as cGMP. although the latter failed to reach significance. 7-NINA and memantine significantly blocked the increase in cGMP evoked by time-dependent sensitisation (TDS)-stress, with PDTC attenuating this response, but not significantly. Additionally, administration of each drug separately for seven days without exposure to stress, did not evoke significant changes in NOx levels, compared to the control group. However, significant increases in cGMP levels, compared to the control group, were found with all four drugs. Repeated trauma therefore activates the NO-cGMP pathway, possibly involving actions on both nNOS and iNOS. The NMDA receptor appears less involved after chronic repeated stress, and may have limited therapeutic implications. Sub-cellular NO-modulation, however, may represent an important therapeutic strategy in preventing the effects of severe stress and in treating PTSD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

Posttraumatic stress disorder (PTSD) is a severe anxiety disorder characterised by hypothalamic-pituitary-adrenal (HPA)-axis abnormalities, hyperarousal, anxiety, flashbacks of trauma memories and avoidance. Increasing evidence is now accumulating that the disorder is also associated with shrinkage of the hippocampus and cognitive dysfunction that may have its origin in stress-induced excitotoxicity. Animal studies have indeed highlighted a potential role of the excitotoxic glutamatenitric oxide (NO) pathway in the stress response. Since PTSD appears to be an illness that progresses and worsens over time after an initial severe traumatic event, this study has used an animal model that emphasises repeated trauma to investigate the effect of stress on hippocampal NO synthase (NOS) activity, the release of the nitrogen oxide metabolites of NO (NOx), and also the evoked release of cGMP. Furthermore, the modulation and dependency of these responses on glutamate, NO and cGMP activity using drugs selective for these targets, will also be investigated. Rats (n=10/group) were exposed to repeated stress together with saline or drug administration immediately after the stress procedure and continuing for one week post-stress. The animals were then sacrificed for assay of hippocampal NOS activity, NO, and cGMP accumulation. Animals received either the glutamate-NMDA receptor antagonist, memantine (MEM;5mg/kg ip/d), the neuronal NOS selective inhibitor, 7- nitroindazole monosodium salt (7-NINA;20mg/kg ip/d), the cGMP-specific PDE inhibitor, sildenafil (SIL;10mg/kg ip/d) or the NFkb antagonist, pyrollidine dithiocarbamate (PDTC;70mg/kg ip/d). The latter inhibits the nuclear transcription factor, NFkb, responsible for inducing the expression of iNOS, while it also appears to mediate the glutamatergic actions on NOS expression, Stress significantly increased hippocampal NOS activity, as well as significantly increased hippocampal cGMP and NO, levels. These increases were blocked by pretreatment with either PDTC or 7-NINA, while memantine was without effect. Sildenafil significantly augmented stress induced NO, accumulation, as well as cGMP. although the latter failed to reach significance. 7-NINA and memantine significantly blocked the increase in cGMP evoked by time-dependent sensitisation (TDS)-stress, with PDTC attenuating this response, but not significantly. Additionally, administration of each drug separately for seven days without exposure to stress, did not evoke significant changes in NOx levels, compared to the control group. However, significant increases in cGMP levels, compared to the control group, were found with all four drugs. Repeated trauma therefore activates the NO-cGMP pathway, possibly involving actions on both nNOS and iNOS. The NMDA receptor appears less involved after chronic repeated stress, and may have limited therapeutic implications. Sub-cellular NO-modulation, however, may represent an important therapeutic strategy in preventing the effects of severe stress and in treating PTSD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

Aims and objectives: The research aims and objectives of this thesis were: (i) to review literature pertaining to different dermal exposure assessment methods; (ii) to assess dermal exposure of refinery workers to nickel and/or cobalt by making use of skin wipes as a removal method; (iii) to assess concurrently the skin condition of the above mentioned workers by measuring skin hydration, transepidermal water loss (TEWL) and skin surface pH, and (iv) to compare South African skin notations and sensitisation notations with those of other developed countries. Methods: Refinery workers from two base metal refineries participated in this study. Skin condition and dermal exposure was measured on different anatomical areas before, during and at the end of a work shift. Dermal exposure to nickel and/or cobalt was assessed with Ghostwipes TM as a removal method. Wipe samples of potentially contaminated surfaces in the workplace were also collected. Wipes were analysed for nickel and/or cobalt according to NIOSH method 9102, using Inductively Coupled Plasma-Atomic Emission Spectrometry. The assignment and use of skin notations and sensitisation notations in South African legislation and six other developed countries were compared. Results: To date, occupational dermal exposure has been reported for numerous substances by making use of surrogate skin methods (interception methods), removal methods and fluorescent tracer methods (in situ detection methods). From published literature it is evident that skin (dermal) wipes, as a removal method, are the most appropriate method to assess dermal exposure to metals. Varying degrees of skin dryness (low hydration indices) and impaired barrier function (high TEWL indices) are reported, with the hands being implicated the most. However, normal skin condition is also reported for some anatomical areas. Skin surface pH for all anatomical areas sampled decreased significantly during the shift, but remained in normal range. Dermal exposure to nickel occurred during the shift at the electro-winning plant of one refinery, while dermal co-exposure to cobalt and nickel occurred at the cobalt plant of the other refinery. At both of the refineries, cobalt and/or nickel was collected from the workers’ skin even before the shift. Also, dermal exposure to these metals was highly variable between individual workers. Skin notations in South African legislation had a mean agreement of between 42.9% and 45.8% with other countries, while agreement for sensitisation notations was only 3.6% between countries. / Thesis (Ph.D. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

Background: Platinum refinery workers are exposed to various elements during the refining process, with soluble platinum salts posing a potential health risk. Platinum salts are extremely potent sensitisers that can result in the clinical syndrome of platinum salt sensitivity (PSS) that leads to skin and respiratory hypersensitivity in refinery workers. Several published research articles document refinery workers’ exposure levels to soluble platinum salts during production. However, the exposure levels to soluble platinum salts during non–routine stock take activities are unknown although cases of sensitisation have been diagnosed following these nonoperational periods. Stock take for the platinum refinery under study commenced on 18 January 2010 and ended 22 February 2010. Increased emphasis was placed on flushing plant equipment rather than dismantling it. The aim was to dismantle 10% of what previously was dismantled to reduce the risk of exposing employees to soluble platinum salts, to reduce the chance of damaging plant equipment and for cost and time saving purposes. Aim: The objectives of this study are to: (i) quantify work area and personal exposure levels; (ii) identify work areas and work practices with exposure levels exceeding the occupational exposure limit (OEL) (>2 ug/m3); (iii) determine whether exposure levels differ significantly between: a) personal sampling groups (engineering versus production), b) area sampling groups (open versus closed–face sampling), c) work areas, d) total area and total personal sampling groups and to (iv) evaluate the efficiency of the current control measures utilised. Design and Method: A total of 58 platinum samples were collected, consisting of 38 personal and 20 area samples. Personal sampling consisted of Institute of Occupational Medicine (IOM) samplers housing reusable 25 mm filter cassettes with mixed cellulose ester (MCE) membrane filters for the collection of inhalable airborne particles. Because both the cassette and the filter were pre and post–weighed as a single unit, all particles collected (even those against the walls of the cassette) were included in the analysis. Sampling was conducted in accordance with the stock take schedule and scope and included a roster for the systematic dismantling and cleaning of the refinery, following the process flow. A target population of maximum five fitters and five operators per area were identified, responsible for dismantling and cleaning plant equipment respectively. The sampling strategy was based on the identification and sampling of employees presumed to have the highest exposure risk. The Occupational Exposure Sampling Strategy Manual (OESSM) refers to this as the “maximum risk employees” (Liedel et al., 1977). The selection of the maximum risk employees was done with reasonable certainty since the employees sampled were working closest to the source of exposure. Sampling was conducted for the total duration of the task consisting of single sample measurements. Area sampling was conducted by means of BUCKAir high volume samplers fitted with preweighed 47 mm MCE filter cassettes to show the spread of the contaminant in the work area. The high volume samplers were calibrated to operate at a sampling volume of 20 L/min. The sampling heads were positioned 1.5 m from the ground surface and as near as possible to the work location or failing this as near as is possible to major sources of exposure. Samples were collected and analysed according to the method for the determination of hazardous substances 46/2 (MDHS 46/2). This is an advanced sampling and analysis standard which enables detection of low levels of soluble platinum (0.01 ug/m3). Results: Thirty eight personal platinum samples were collected, consisting of a sampled engineering (n=15) and production (n=23) subgroup. Out of the thirty eight personal samples taken in total, 21% of the samples’ concentrations exceeded the OEL of 2 ug/m3 and ranged between 0.004–20.479 ug/m3. Twenty area platinum samples were collected, consisting of open (n=10) and closed face (n=10) sampling. Out of the twenty area samples taken in total, 10% of the samples’ concentrations exceeded the OEL of 2 ug/m3 and ranged between 0.0004–5.752 ug/m3. The mean personal exposure levels for the production subgroup (2.739 ug/m3) were significantly higher compared to the engineering subgroup’s mean personal exposure levels (0.393 ug/m3). This significant difference (p=0.033) was expected since the production subgroup was more exposed and involved in the digging out of residues and the cleaning of plant equipment compared to the engineering subgroup with limited exposure and involved in the opening of plant equipment. Although the mean exposure levels for open face sampling (0.725 ug/m3) were higher compared to the mean exposure levels for closed face sampling (0.441 ug/m3) no significant difference (p=0.579) were noted. The mean area exposure levels (0.583 ug/m3) were significantly lower (p=0.004) compared to the mean personal exposure levels (1.813 ug/m3) for similar areas and tasks performed and, therefore, not an effective indicator of personal exposure levels. Higher personal exposure levels were expected since the workers were closer to the source of exposure and since the platinum salts could have diluted in the workplace’s air resulting in lower area exposure levels. Conclusion: The research study addressed the problem statement, met the objectives set out in Chapter 1, hypotheses were accepted and rejected and future studies were recommended. It was hypothesised that: a) refinery workers are exposed to airborne soluble platinum during non–operational periods; b) exposure levels do not differ significantly between the personal sampling groups (engineering vs production); c) exposure levels do not differ significantly between the area sampling groups (open versus closed–face sampling); d) exposure levels do not differ significantly between work areas; e) exposure levels differ significantly between total personal and total area sampling groups. The results confirmed that refinery workers are exposed to airborne soluble platinum during non–operational periods and hypothesis a was accepted. The personal exposure levels of the engineering versus production sampling groups differed statistically (p=0.033) and hypothesis b was rejected. The exposure levels of the open and closed face sampling groups did not differ significantly (p=0.579) and hypothesis c was accepted. In addition no statistical difference (p>0.05) was indicated between the work areas and hypothesis d was accepted. Total personal versus total area exposure levels (p=0.004) differed statistically and hypothesis e was accepted. / Thesis (M.Sc. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

Aims and objectives: The research aims and objectives of this thesis were: (i) to review literature pertaining to different dermal exposure assessment methods; (ii) to assess dermal exposure of refinery workers to nickel and/or cobalt by making use of skin wipes as a removal method; (iii) to assess concurrently the skin condition of the above mentioned workers by measuring skin hydration, transepidermal water loss (TEWL) and skin surface pH, and (iv) to compare South African skin notations and sensitisation notations with those of other developed countries. Methods: Refinery workers from two base metal refineries participated in this study. Skin condition and dermal exposure was measured on different anatomical areas before, during and at the end of a work shift. Dermal exposure to nickel and/or cobalt was assessed with Ghostwipes TM as a removal method. Wipe samples of potentially contaminated surfaces in the workplace were also collected. Wipes were analysed for nickel and/or cobalt according to NIOSH method 9102, using Inductively Coupled Plasma-Atomic Emission Spectrometry. The assignment and use of skin notations and sensitisation notations in South African legislation and six other developed countries were compared. Results: To date, occupational dermal exposure has been reported for numerous substances by making use of surrogate skin methods (interception methods), removal methods and fluorescent tracer methods (in situ detection methods). From published literature it is evident that skin (dermal) wipes, as a removal method, are the most appropriate method to assess dermal exposure to metals. Varying degrees of skin dryness (low hydration indices) and impaired barrier function (high TEWL indices) are reported, with the hands being implicated the most. However, normal skin condition is also reported for some anatomical areas. Skin surface pH for all anatomical areas sampled decreased significantly during the shift, but remained in normal range. Dermal exposure to nickel occurred during the shift at the electro-winning plant of one refinery, while dermal co-exposure to cobalt and nickel occurred at the cobalt plant of the other refinery. At both of the refineries, cobalt and/or nickel was collected from the workers’ skin even before the shift. Also, dermal exposure to these metals was highly variable between individual workers. Skin notations in South African legislation had a mean agreement of between 42.9% and 45.8% with other countries, while agreement for sensitisation notations was only 3.6% between countries. / Thesis (Ph.D. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

Background: Platinum refinery workers are exposed to various elements during the refining process, with soluble platinum salts posing a potential health risk. Platinum salts are extremely potent sensitisers that can result in the clinical syndrome of platinum salt sensitivity (PSS) that leads to skin and respiratory hypersensitivity in refinery workers. Several published research articles document refinery workers’ exposure levels to soluble platinum salts during production. However, the exposure levels to soluble platinum salts during non–routine stock take activities are unknown although cases of sensitisation have been diagnosed following these nonoperational periods. Stock take for the platinum refinery under study commenced on 18 January 2010 and ended 22 February 2010. Increased emphasis was placed on flushing plant equipment rather than dismantling it. The aim was to dismantle 10% of what previously was dismantled to reduce the risk of exposing employees to soluble platinum salts, to reduce the chance of damaging plant equipment and for cost and time saving purposes. Aim: The objectives of this study are to: (i) quantify work area and personal exposure levels; (ii) identify work areas and work practices with exposure levels exceeding the occupational exposure limit (OEL) (>2 ug/m3); (iii) determine whether exposure levels differ significantly between: a) personal sampling groups (engineering versus production), b) area sampling groups (open versus closed–face sampling), c) work areas, d) total area and total personal sampling groups and to (iv) evaluate the efficiency of the current control measures utilised. Design and Method: A total of 58 platinum samples were collected, consisting of 38 personal and 20 area samples. Personal sampling consisted of Institute of Occupational Medicine (IOM) samplers housing reusable 25 mm filter cassettes with mixed cellulose ester (MCE) membrane filters for the collection of inhalable airborne particles. Because both the cassette and the filter were pre and post–weighed as a single unit, all particles collected (even those against the walls of the cassette) were included in the analysis. Sampling was conducted in accordance with the stock take schedule and scope and included a roster for the systematic dismantling and cleaning of the refinery, following the process flow. A target population of maximum five fitters and five operators per area were identified, responsible for dismantling and cleaning plant equipment respectively. The sampling strategy was based on the identification and sampling of employees presumed to have the highest exposure risk. The Occupational Exposure Sampling Strategy Manual (OESSM) refers to this as the “maximum risk employees” (Liedel et al., 1977). The selection of the maximum risk employees was done with reasonable certainty since the employees sampled were working closest to the source of exposure. Sampling was conducted for the total duration of the task consisting of single sample measurements. Area sampling was conducted by means of BUCKAir high volume samplers fitted with preweighed 47 mm MCE filter cassettes to show the spread of the contaminant in the work area. The high volume samplers were calibrated to operate at a sampling volume of 20 L/min. The sampling heads were positioned 1.5 m from the ground surface and as near as possible to the work location or failing this as near as is possible to major sources of exposure. Samples were collected and analysed according to the method for the determination of hazardous substances 46/2 (MDHS 46/2). This is an advanced sampling and analysis standard which enables detection of low levels of soluble platinum (0.01 ug/m3). Results: Thirty eight personal platinum samples were collected, consisting of a sampled engineering (n=15) and production (n=23) subgroup. Out of the thirty eight personal samples taken in total, 21% of the samples’ concentrations exceeded the OEL of 2 ug/m3 and ranged between 0.004–20.479 ug/m3. Twenty area platinum samples were collected, consisting of open (n=10) and closed face (n=10) sampling. Out of the twenty area samples taken in total, 10% of the samples’ concentrations exceeded the OEL of 2 ug/m3 and ranged between 0.0004–5.752 ug/m3. The mean personal exposure levels for the production subgroup (2.739 ug/m3) were significantly higher compared to the engineering subgroup’s mean personal exposure levels (0.393 ug/m3). This significant difference (p=0.033) was expected since the production subgroup was more exposed and involved in the digging out of residues and the cleaning of plant equipment compared to the engineering subgroup with limited exposure and involved in the opening of plant equipment. Although the mean exposure levels for open face sampling (0.725 ug/m3) were higher compared to the mean exposure levels for closed face sampling (0.441 ug/m3) no significant difference (p=0.579) were noted. The mean area exposure levels (0.583 ug/m3) were significantly lower (p=0.004) compared to the mean personal exposure levels (1.813 ug/m3) for similar areas and tasks performed and, therefore, not an effective indicator of personal exposure levels. Higher personal exposure levels were expected since the workers were closer to the source of exposure and since the platinum salts could have diluted in the workplace’s air resulting in lower area exposure levels. Conclusion: The research study addressed the problem statement, met the objectives set out in Chapter 1, hypotheses were accepted and rejected and future studies were recommended. It was hypothesised that: a) refinery workers are exposed to airborne soluble platinum during non–operational periods; b) exposure levels do not differ significantly between the personal sampling groups (engineering vs production); c) exposure levels do not differ significantly between the area sampling groups (open versus closed–face sampling); d) exposure levels do not differ significantly between work areas; e) exposure levels differ significantly between total personal and total area sampling groups. The results confirmed that refinery workers are exposed to airborne soluble platinum during non–operational periods and hypothesis a was accepted. The personal exposure levels of the engineering versus production sampling groups differed statistically (p=0.033) and hypothesis b was rejected. The exposure levels of the open and closed face sampling groups did not differ significantly (p=0.579) and hypothesis c was accepted. In addition no statistical difference (p>0.05) was indicated between the work areas and hypothesis d was accepted. Total personal versus total area exposure levels (p=0.004) differed statistically and hypothesis e was accepted. / Thesis (M.Sc. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

Background: Workers in a platinum group metals (PGMs) refinery are potentially exposed to various precious metals (iridium, osmium, palladium, platinum, rhodium and ruthenium) and their metal-salt compounds which may cause rhinitis, asthma, contact urticaria and conjunctivitis. Some cases revealed that sensitisation occurred in employees where it was not possible to detect any airborne soluble platinum or where the respiratory soluble platinum exposure was below the occupational exposure limit. It is unclear whether respiratory exposure or a combination of respiratory and dermal exposure may be involved in sensitisation and the possible elicitation of skin symptoms. Objectives: To determine if dermal exposure to PGMs took place during the refining process and in the administration area by using a removal method and to compare dermal exposure on the different anatomical areas and in two different working areas, Areas A and B for each of the PGMs. Methods: Dermal exposure samples were collected with a removal method using GhostwipesTM. The samples were collected from the palm of the hands, the wrists and the necks of the workers, before the shift started, before tea time, before lunch time and after the shift ended. The skin wipes were analysed for the PGMs (iridium, osmium, palladium, platinum, ruthenium and rhodium) according to Methods for the Determination of Hazardous Substances (MDHS) method 46/2, using Inductively Coupled Plasma-Mass Spectrometry. Results: No published data is available on occupational dermal exposure to PGMs in a precious metals refinery. This study proved that dermal exposure to PGMs in the refinery took place and was quantified. The PGM dermal exposure results in general, were very low (measured in nano grams), with platinum having the overall highest exposure. Exposure also occurred the most frequently during the last two intervals of the day, before lunch time and at the end of the shift. Exposure on all three the anatomical areas that were tested in the study, varied much with the palm of the hands having the highest exposure levels. There were also variations in exposure between areas A and B due to the fact that the processes in these two areas differ. Conclusions: It was confirmed that dermal exposure to PGMs took place at the precious metals refinery. The highest exposure took place before lunch time and towards the end of the shift. The metal to which the workers were exposed the most was platinum and the production area where the workers had the highest exposure to most of the metals was Area B. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2015

Background: Workers in a platinum group metals (PGMs) refinery are potentially exposed to various precious metals (iridium, osmium, palladium, platinum, rhodium and ruthenium) and their metal-salt compounds which may cause rhinitis, asthma, contact urticaria and conjunctivitis. Some cases revealed that sensitisation occurred in employees where it was not possible to detect any airborne soluble platinum or where the respiratory soluble platinum exposure was below the occupational exposure limit. It is unclear whether respiratory exposure or a combination of respiratory and dermal exposure may be involved in sensitisation and the possible elicitation of skin symptoms. Objectives: To determine if dermal exposure to PGMs took place during the refining process and in the administration area by using a removal method and to compare dermal exposure on the different anatomical areas and in two different working areas, Areas A and B for each of the PGMs. Methods: Dermal exposure samples were collected with a removal method using GhostwipesTM. The samples were collected from the palm of the hands, the wrists and the necks of the workers, before the shift started, before tea time, before lunch time and after the shift ended. The skin wipes were analysed for the PGMs (iridium, osmium, palladium, platinum, ruthenium and rhodium) according to Methods for the Determination of Hazardous Substances (MDHS) method 46/2, using Inductively Coupled Plasma-Mass Spectrometry. Results: No published data is available on occupational dermal exposure to PGMs in a precious metals refinery. This study proved that dermal exposure to PGMs in the refinery took place and was quantified. The PGM dermal exposure results in general, were very low (measured in nano grams), with platinum having the overall highest exposure. Exposure also occurred the most frequently during the last two intervals of the day, before lunch time and at the end of the shift. Exposure on all three the anatomical areas that were tested in the study, varied much with the palm of the hands having the highest exposure levels. There were also variations in exposure between areas A and B due to the fact that the processes in these two areas differ. Conclusions: It was confirmed that dermal exposure to PGMs took place at the precious metals refinery. The highest exposure took place before lunch time and towards the end of the shift. The metal to which the workers were exposed the most was platinum and the production area where the workers had the highest exposure to most of the metals was Area B. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2015

Posttraumatic stress disorder (PTSD) is classified as an anxiety disorder and the characteristic symptoms (re-experiencing, avoidance as well as numbing of general responsiveness and hyperarousal) of this disorder develop in response to a traumatic event. The disorder is characterised by hypothalamic-pituitary-adrenal (HPA) axis abnormalities linked with changes in cortisol moreover, the hippocampus and cortex also play a role in the neurobiology. With regard to the neurochemistry of this disorder it is known that gamma amino butyric acid (GABA) is involved however, the precise role of GABA in PTSD and how stress changes GABA concentrations in the brain are still not fully understood. Another aspect regarding PTSD that has not been clearly defined is the treatment of PTSD. Classic anxiolytics such as diazepam is expected to relieve the anxiety linked with PTSD. Studies with this group of drugs have however not produced the concrete evidence needed to establish it as a treatment of choice for PTSD and subsequently other classes of drugs have been investigated as possible treatment options for PTSD. Among these is lamotrigine, which in a clinical study was found to be effective in alleviating symptoms of PTSD. Moreover, a possible pharmacokinetic-pharmacodynamic relationship for each of these drugs has also not been elucidated. In order to elude on some of these uncertainties, an animal model of PTSD, time dependent sensitisation (TDS), was used. GABA levels in the rat hippocampus and frontal cortex were determined at two different time intervals following the TDS procedure (1 day and 7 days post re-stress). High performance liquid chromatography (HPLC) with electrochemical (EC) detection was used to determine gamma amino butyric acid (GABA) concentrations. To investigate the possible anxiolytic effects of diazepam and lamotrigine in this model, as well as a possible pharmacokinetic-pharmacodynamic relationship for each drug, pharmacokinetic profiles for both drugs were established in order to find the times of peak and trough levels of each drug. Blood samples were collected at different time intervals after drug administration either from the tail vein of rats (lamotrigine) or directly from the heart (diazepam). Subsequently, drug concentrations at each time interval were determined by means of HPLC with ultraviolet (UV) detection. The behaviour of rats was analysed using the elevated plus-maze (EPM) at peak or trough concentrations of the drugs and this was performed after either acute administration of the drug, or after a 14 day chronic treatment regime. GABA levels in the hippocampus were not found to change statistically significantly in response to stress at either 1 day or 7 days post re-stress. In the frontal cortex, however, GABA levels increased in response to stress at 1 day post re-stress, with a statistically insignificant, but strong trend towards an increase, at 7 days post re-stress. With regard to the pharmacokinetic profiles, the peak concentration of diazepam was found to occur at 60 minutes, with lamotrigine's peak at 120 minutes. The behavioural studies indicated that acute treatment with diazepam 3 mg/kg resulted in a statistically significant increase in both ratio open arm entries and ratio time spent in the open arms at peak level of the drug. After acute treatment with diazepam 3 mg/kg a statistically significant decrease in ratio time spent in open arms was also found when the ratio time spent in open arms at peak level of the drug and the ratio time spent in open arms at trough level of the drug was compared. In response to chronic treatment with diazepam 3 mg/kg for 14 days, test animals exhibited an increase in the ratio open arm entries at trough level of the drug, with a statistically insignificant yet definite trend towards an increase at peak level. Acute treatment with lamotrigine 10 mg/kg resulted in no statistically significant change in EPM parameters. In response to chronic treatment, however, a statistically significant increase was found in ratio time spent in open arms at peak level of the drug, with a statistically insignificant trend towards an increase at trough level. From the results of this study, we may therefore conclude that GABA-levels in the brain are definitely affected, but in different ways, following TDS-stress. A pharmacokinetic-pharmacodynamic relationship between the drugs' levels and aversive behaviour could also be established. Furthermore it appears that more sustained anxiolytic effects are evident following chronic treatment with both drugs than with acute administration of these drugs. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2006