Wheat is the biggest winter cereal crop in South Africa and the second largest cereal to feed the population of South Africa. The population of South Africa grows with approximately one million people a year. Consistent wheat production is necessary for food security and is therefore of extreme agricultural and economic significance. Future production increases depend on the ability to improve, or at least maintain, the rate of increase to feed the population. The study was undertaken to investigate genetic improvement (genetic advance) in wheat by various statistical methods of analysis. This was done to determine the most suitable procedure to evaluate genetic improvement in the three wheat production areas of South Africa, namely the Western Cape province, the Free State province and the irrigation areas. The second objective of this study was to demonstrate the trend of yield and the two quality traits [HLM (hectolitre mass) and protein content] over 16 years (1995-2010) by various statistical techniques. The third objective was to compare the AMMI (additive main effects and multiplicative interaction) and the GGE (genotype plus genotype-by-environment interaction) analyses in assessing genotype-by-environment interaction (GEI) for yield and the two quality traits. The fourth objective was to study the relationship among wheat grain yield and the two quality traits by various statistical techniques. Linear regression (TRET) and various variance component methods were investigated to determine genetic advance. The recommended method of determining genetic advance in this study is TRET. In the Western Cape elite trials TRET predicted a genetic advance of 1% per year and genetic advance estimated at 1% genetic improvement for protein content in the cultivar trials. No significant trend was observed in the elite trials of the Free State with TRET. Yield showed 0.5% and 0.6% per year improvement for the two planting dates of the eastern cultivar trials of Free State. A yield improvement of 0.3% per year improvement for the two planting dates of the central cultivar trials of Free State was determined. A genetic advance for yield of 0.7% per year was found in the warm region of the elite irrigation trials and 9% yield improvement per year for the first planting date of the eastern region of the cultivar irrigation trials. A negative trend was observed for the second planting date of eastern region of both elite and cultivar irrigation trials. 172 The effects of GEI on yield and quality traits were studied by comparing the AMMI and GGE analyses. These methods portrayed similar results. An advantage of these techniques is their complementary nature. Although both models portray GEI in various biplots, the AMMI provides statistical evidence to the visual presentation of the GGE biplots. Pearson product moment correlation matrix provided a linear relationship among the variables studied. Principal component analysis (PCA), cluster analysis (CA) and discriminant analysis (DA) offered auxiliary information on the relationship among the factors (e.g. genotypes, years, localities and/or environments) and the variables. DA was not able to indicate direction of genetic improvement in either of the three production areas in this study.

Wheat (Triticum aestivum) is one of the most important cereal crops worldwide and cultivated in a wide range of environments. The production of wheat, based on consumption and other demands, needs to be increased to meet the annual requirements for its domesticated uses. Wheat productivity is influenced by biotic and abiotic stresses. Therefore, appropriate, efficient and environmentally friendly control measures to lessen such stresses need to be applied. Fungal diseases of wheat, including leaf rust, stripe rust, stem rust, powdery mildew and Fusarium head blight (FHB) can cause yield losses. The diseases result in a reduction in grain yield and affect grain quality negatively. The use of resistant cultivars is an effective, economical and environmentally safe approach to lower fungicide dependence and to reduce production losses due to foliar diseases. In this study, we combined rust and FHB resistance genes and/or quantitative trait loci (QTL) and molecular marker analyses were applied using polymorphic microsatellites (simple sequence repeats, SSR). The aim of the study was to combine five rust resistance genes (against leaf, stem and stripe rust) and five FHB resistance genes/QTL for type I and II resistance into a single wheat genotype with the aid of both marker-assisted and phenotypic selection. Molecular markers used in the study are already being used in commercial breeding programmes in South Africa. The study was divided into two phases. Phase one was aimed at combining rust resistance genes/QTL into a single genotype using parental lines AvocetYrSp, Blade, Kariega and CSLr19-149-299 and to select the best lines based on the number and combination of homozygous genes/QTL present. The genes Sr2, Sr26, Lr19, Lr34/Yr18/Sr57 and QTL QYr.sgi-2B were sourced from parental lines and combined in a double cross breeding scheme followed by several rounds of selfing. Selection was done using marker-assisted selection (MAS). The two best rust resistant lines were selected. Line S16(7.3) contained QYr.sgi-2B.1, Lr34/Yr18/Sr57 and Lr19 in a homozygous state while line S726(3.2) contained Lr34/Yr18/Sr57 and Lr19 in a homozygous and Sr26 in a heterozygous state. Phenotypic screening furthermore indicated the presence of YrSp in line S726(3.2). FHB resistance QTL for the second phase of the project were sourced from Frontana (type I resistance) and CM-82036 (type II resistance). The FHB resistant lines were crossed with the two best rust resistant lines in a double cross breeding scheme and selection was done using molecular markers. The study was conducted over a period of three years. A total of 954 individuals of a double cross population were screened with five markers associated with rust resistance genes/QTL and five markers associated with FHB resistance QTL. The following markers were used to screen for accumulated rust resistance genes/QTL: cssfr5 (Lr34/Yr18/Sr57), Gwm148 and Gwm501 (QYr.sgi-2B.1), STSLr19130 (Lr19) and Sr26#43 (Sr26). The markers DuPw227 (3A), Barc133 (3B), Gwm156, Gwm293 and Barc197.2 (5A), Gwm133 and Gwm644 (6B) and Gwm233 (7A) were used to identify individuals containing FHB resistance QTL. The number of resistance markers in the double cross family ranged between one to nine out of the 10 tested markers. The two best lines, 116.3 and 123.1, contained all markers except the marker linked to the minor FHB QTL on chromosome 7A. All tested lines contained Lr34/Yr18/Sr57 in a homozygous state while all other markers were segregating. The best lines will be self-pollinated for use in future breeding programmes.

Induced mutation was incorporated into the South African sweet potato breeding programme to improve elite cultivars for yield, drought adaptation and nutritional quality. Three cream-fleshed cultivars namely Ndou, Monate and Mokone were selected, propagated in vitro and subjected to gamma ray mutagenesis from a 60Co source at SANBS. Radio-sensitivity tests were done on three node cuttings used as explants to determine optimum dosages for bulk irradiation. Data was subjected to regression analysis and calculated LD50 values were 64 Gy for Ndou, 38 Gy for Monate and 55 Gy for Mokone. Variation observed in lethal dosages highlighted the importance to test each genotype or plant material for sensitivity before mutagenic treatment. Bulk irradiation was done at respective optimum dosages and explants were propagated in vitro up to M1V4 and M2V5 stages to dissolve chimeras and obtain stable mutations. Three mutant populations comprised of 8 207 mutant plants were generated. These mutant plants were screened in the glasshouse for phenotypic/morphological changes visible to the naked eye. Mutant plants with changes in leaf shape, vine colour, fused veins, abaxial vein pigmentation, chlorophyll variegation on leaves and root flesh colour from cream to pale orange/yellow, were observed. After screening, 410 mutant plants (4.99%) with phenotypic changes were identified from the generated mutant populations. Mutant plants/lines derived from the cultivar Ndou were further subjected to vegetative drought and heat tolerance screening in the glasshouse. Two experiments were conducted and these mutant lines were evaluated for drought tolerance and drought and heat tolerance respectively. Thirteen mutant lines with improved drought and heat tolerance, when compared to Ndou, were identified from the first experiment. Further drought screening procedures will be conducted to confirm these results. Field evaluation trials were established to evaluate Ndou mutant lines. These were first evaluated in an initial evaluation trial at Lwamondo using single plants established from seedlings in a non-balanced completely randomised design. Mutant lines with three replicates each were harvested, data was collected on root yield and samples were taken and freeze dried for mineral and total starch content analyses. No mutant line had significantly improved root yields compared to Ndou. Thirteen mutant lines with significantly improved Mn and six mutant lines with significantly improved Mg contents compared to Ndou were identified. Total starch contents were significantly higher in four mutant lines than that of Ndou. Non-significant variations were observed in Zn and Fe contents between mutant lines and the control. Promising mutant lines were further identified and evaluated in a replicated preliminary yield evaluation trial at Towoomba. Top cuttings were used to establish the trial. Data was collected on marketable yield, unmarketable yield, total yield, root-flesh colour and dry mass content. Two mutant lines, M96 and M95, had improved total yields of 33.01 t ha-1 and 30.02 t ha-1 respectively compared to Ndou with 22.96 t ha-1. Dry mass contents were also improved in two mutant lines M47 (30.33%) and M28 (29.38%) compared to the control Ndou (27.00%). Root flesh colour changes were identified phenotypically in M224 and M6 with changes from cream to pale orange/yellow. All mutant lines will be subjected to advanced yield and nutrient evaluations including β- carotene quantification to identify mutant lines with improved yield, drought adaptation and enhanced nutritional contents to address food security and micronutrient deficiency in SA.

Buffalo-adapted Theileria parva causes Corridor disease in cattle. Strict control measures therefore apply to the movement of buffalo in South Africa and include mandatory testing of buffalo for the presence of T. parva. The official test is a real-time hybridization PCR assay that amplifies the V4 hypervariable region of the 18S rRNA gene of T. parva, T. sp. (buffalo) and T. sp. (bougasvlei). The effect that mixed T. parva and T. sp. (buffalo)-like infections have on accurate T. parva diagnosis was investigated. In-vitro mixed infection simulations indicated PCR signal suppression at 100 to 1000-fold T. sp. (buffalo) excess at low T. parva parasitaemia. Suppression of PCR signal was found in field buffalo with mixed infections. The T. parva-positive status of these cases was confirmed by selective suppression of T. sp. (buffalo) amplification using a locked nucleic acid clamp and independent assays based on the p67, p104 and Tpr genes. Conventional and SYBR® Green touch-down PCR methods were developed for each protein coding gene and buffalo from the endemic Kruger National Park were screened. The protein gene assays compared well with the negative and T. parva positive samples diagnosed on the current real-time assay however, they did detect additional positive samples diagnosed as negative on the real-time hybridization. These samples were all T. sp. (buffalo) positive. This confirmed the suppressive effect on PCR signal due to template competition in the current real-time PCR assay. Some positive samples were not detected by the protein genes, possibly due to sequence variation in the primer regions. These independent markers proved useful as supplementary assays in the accurate diagnosis of T. parva infections where mixed infections occur in the buffalo host. The development of the Hybrid II assay, a real-time hybridization PCR method, which compared well with the official hybridization assay in terms of specificity and sensitivity revolutionized the diagnosis of the disease for the main reason that it is not influenced by mixed infections of T. sp. (buffalo)-like parasites and is as such a significant improvement on the current hybridization assay. While the incidence of mixed infections in the Corridor disease endemic region of South Africa is significant, little information is available on the specific distribution and prevalence of T. sp. (buffalo) and T. sp. (bougasvlei). Specific real-time PCR assays were developed and a total of 1211 samples known to harbor these parasites were screened. Both parasites are widely distributed in southern Africa and the incidence of mixed infections with T. parva within the endemic region is similar (~25-50%). However, a significant discrepancy exists with regard to mixed infections of T. sp. (buffalo) and T. sp. (bougasvlei) (~10%). Evidence for speciation between T. sp. (buffalo) and T. sp. (bougasvlei) is supported by phylogenetic analysis of the COI gene, and their designation as different species. This suggests mutual exclusion of parasites and the possibility of hybrid sterility in cases of mixed infections.

African animal trypanosomiasis (AAT) is a disease caused by haemoparasites of the genus Trypanosoma and its vectors are tsetse flies of the genus Glossina which are endemic to the African continent. In South Africa the disease is restricted to the north eastern parts of KwaZulu-Natal Province and it is transmitted to susceptible vertebrate hosts by Glossina brevipalpis and G. austeni. The current study aimed at determining the prevalence, genetic diversity and the phylogenetic position of the South African trypanosome species in the north eastern KwaZulu-Natal as well as determining preferred feeding host by tsetse flies from their blood meal. A total of 296 blood samples were collected from the north eastern parts of KwaZulu-Natal Province whereby 137 were from cattle; 101; 9; 49 were from goats, sheep and dogs respectively and 376 tsetse flies (375 G. brevipalpis and 1 G. austeni) were also collected. PCR with universal KIN primers was used to detect the trypanosome parasites in both blood and tsetse flies. From 137 cattle samples 23.4% (32/137) were positive for the presence of trypanosome infections whilst none were positive for sheep, goat and dog samples. A total of 15.4% (54/375) G. brevipalpis tested positive for trypanosomes. Detected trypanosome species with KIN primers were Trypanosoma congolense (Savannah) and T. theileri for blood samples and for tsetse flies T. congolense (Savannah and Kilifi) types were detected. Nested PCR targeting 18S rRNA gene detected T. congolense (Savannah) and T. theileri species. The sequences from this gene revealed great genetic diversity within these Trypanosoma species. Amplification of gGAPDH gene detected T. congolense (Savannah) and T. brucei brucei species when subjected to BLAST. Sequences obtained from this gene also revealed great genetic diversity and showed that the detected trypanosomes are different genotypes from the known species in other countries outside South Africa. Phylogenetic analysis revealed that South African Trypanosoma species were more genetically related to east African trypanosomes however, they formed isolated clusters with each other indicating that indeed they are different genotypes from the trypanosome species on the NCBI database. Blood meal analysis showed that G. brevipalpis preferred to feed on small mammals, birds and humans in the absence of livestock or other large wild reservoir hosts. This study showed that there are active trypanosomes circulating amongst livestock and tsetse flies in KwaZulu-Natal Province as well as the prevalence of T. theileri and T. b. brucei which were never documented in previous studies. Further research is needed to investigate the pathogenicity of these detected Trypanosoma parasites in domestic animals.

The use of urban wastewater for agriculture crop production is receiving renewed attention in most parts of the world due to the increasing scarcity of water. Water scarcity has placed pressure on the ability of households to meet their basic needs as the intermittent supply of water has created a demand for other sources of water, such as wastewater for irrigation, which can either be expensive or dangerous to public health. In this regard it might seem obvious to view wastewater as a major source of water for Bulawayo, Zimbabwe, particularly for irrigation. The general objective of the study was to characterise and determine treated domestic wastewater parameters that are of agricultural, public health and environmental importance for use in urban agriculture irrigation in Bulawayo. The study critically assessed the wastewater quality being used for urban agriculture in relation to its characteristics, the possible impacts on environment health and also quantifying the socio economic factors that can be derived from its use and, based on this assessment, to formulate a strategy for sustainable treated domestic wastewater use for irrigation. Data collection for this study was conducted in Bulawayo urban area and the gum plantation from 2005 - 2010. Extensive wastewater quality analysis was carried out and results of effluent analysis of key parameters, nitrogen and phosphorous were found to be 11.5 mg/l ± 4.4 and 13.5 mg/l ±14.9 respectively, which were within the World Health Organisation (WHO) (2006) acceptable range. These results aided to confirm that the treated domestic wastewater is of acceptable quality and hence has potential to be used for irrigating crops such as maize, beans and vegetables (chomolier) with minimal risk. Effluent heavy metals concentration in the form of Cadmium (Cd) and lead (Pb) measured values of 0.027 mg/l ± 0.01 and 0.45 mg/l respectively and were within the acceptable levels according to the WHO guidelines and Zimbabwe National Water Authority (ZINWA) standards. Heavy metal soil content was also observed to be within the acceptable limits with both Cd and Pb showing strong correlation with soil pH (r2= 1). Vegetable tissue analysis did not detect any significant levels of Cd and Pb in vegetable samples including Chomolier (not detected),maize (not detected), and beans (not detected), which then confirmed the conclusion that the treated domestic wastewater has potential for agricultural irrigation provided the quality of the effluent would not change drastically from the observed status which was measured over five years. With regard to social acceptance and economic benefits, the study revealed that acceptance for use of treated domestic wastewater and consumption of produce from its use was high amongst the farmers with 88.9% of respondents acknowledging no problem in using the treated domestic wastewater. Estimation of financial benefits were derived using the conventional market based approach which then revealed that an income of about US$1000 per plot/year is feasible if a proper management system is put in place. Findings of this study confirm that use of treated domestic wastewater for urban irrigation can improve livelihoods of the resource limited farmers despite the health challenges associated with its use. Majority of the famers reported that use of treated domestic wastewater for agriculture has contributed significantly to their socio- economic lifestyles by making extra income to cover school fees (44.6%), medication (9.85%) and food (99.1%). Apart from the financial benefits observed, calculations using the FAO formula for nutrient contribution, the study indicated that the treated domestic wastewater which was used contributed approximately 92 kg/ha/year, 108 kg/ha/year and 281.6 kg/ha/year of nitrogen, phosphorus and potassium respectively hence improving soil fertility of the sandy loam soils found at the farming area. Evaluation of the findings in relation to the recommended guidelines and standards of Food and Agricultural Organisation (FAO)/WHO and ZINWA suggests that the treated domestic wastewater used at the gum plantation is suitable for crop irrigation specifically for the following crops: chomolier, maize and beans that were investigated over time. In addition the benefits of using the treated domestic wastewater were noted to have the potential to enhance proper management of wastewater irrigation as proposed in the strategy as it proved to be a reliable water resource. Adherence to the strategy that is proposed in this thesis of involving stakeholders, addressing policy and legal issues, supporting research and outreach, marketing and periodic monitoring of effluent, soil and plant quality parameters will ensure successful, safe, long-term wastewater irrigation that will balance human and environmental needs.

Cotyledon orbiculata, Hermannia depressa and Nicotiana glauca are widely used plants in traditional medicine for treatment of various infections and diseases. C. orbiculata is mostly used in treatment of epilepsy, earache and the removal of warts while H. depressa is used to relieve toothache, nerves and diarrhoea. Lastly, N. glauca has been mostly used as pain killer in relieving earache, toothache and seldom applied on body in treatment of soreness and inflammation. Traditional usages of these plants by indigenous people and local traditional healers have not yet been scientifically reported, that is why the current study was aimed at determining the anthelmintic and anticancer activity of these plants. The anthelmintic activity of acetone and water extracts from the shoots of Cotyledon orbiculata, Hermannia depressa and Nicotiana glauca were investigated using the egg hatch, larval development and larval mortality assays. In all extracts tested, C. orbiculata water extract at 7.5 mg/ml prevented nematode eggs from hatching with 82.63% success rate. Other extracts exhibited egg hatch inhibition in a degree of less than 50%. Similarly, C. orbiculata water extracts suppressed nematode larval development with 85.32% at the concentration of 2.5 mg/ml followed by 66.69% of H. depressa extract at 7.5 mg/ml concentration. However, N. glauca water and all acetone extracts induced the 100% larval development inhibition. The in vitro larval mortality rate revealed that the water extracts from all the plants were able to kill all larvae at 2.5 mg/ml within 48 to 96 h. The results from this study have shown that the extracts from the three plants have the potential to prevent and ameliorate diseases associated with gastrointestinal nematodes. The anticancer activity of the above mentioned plants was tested on two cancer cell lines, the MCF-7 and HeLa cells. All plants possessed anticancer activity at different durations and concentrations. The N. glauca demonstrated an activity against both cell lines, however, the plant acetone extracts were much effective on the MCF-7 line at 48 hours with inhibition percentages > 80% at all concentrations. The N. glauca acetone extracts were effective at 24 hours. The H. depressa acetone extracts also possessed much activity than water extracts at 24 hours, whereas C. orbiculata showed no activity at all on this cell line. The C. orbiculata acetone extracts followed by the water extracts were the most effective on the HeLa line ranging from 12 to 84% and 0 to 77% inhibition. H. depressa activity was observed at 48 hours of experimentation at all concentrations in both extracts. N. glauca exhibited significant inhibition percentages at 24 hours of water extracts and 48 hours of acetone extracts. This study has showed that the three plants are potential candidates for cancer treatment. Brine shrimp lethality test was conducted on the nauplii stage of the shrimps. Furthermore, two assays, MTT and LDH cytotoxicity assays were conducted on the MDBK cells. None of the plants was toxic on the brine shrimps as most of them survived through 24 and 48 hours. C. orbiculata and H. depressa brine shrimp larval mortality was observed at 96, 72, 72, 96 and 96 h at 0.2, 0.4, 0.6, 0.8, and 1.0 mg/ml of water extracts respectively and 72 h at all concentrations of acetone extracts while N. glauca larval mortality was observed at 120 and 96 hours at all concentration of both extracts. There was a cell survival decrease of 50% at 0.65 mg/ml and 50-60% in C. orbiculata water and acetone extracts treated wells, respectively. No significant cell decrease was observed from both H. depressa and N. glauca water and acetone extracts except for N. glauca acetone extract at 2.50 mg/ml. None of the plants induced a significant toxicity on both the brine shrimps and the bovine cells. Alkaloids, saponins, tannins and phenols were the constituents tested for in order to identify constituents responsible for observed activity of the whole study. No alkaloids were detected from all plants for both extracts, only saponins, tannins and phenols were present even though N. glauca acetone extracts possessed none of the tested constituents. Tested plants are therefore good candidates in treating parasitic gastrointestinal nematodes and cancer disease. Potassium permanganate (KMnOâ) is a widely used chemical substance in the rural communities as prophylaxis or in treatment of various infections and diseases; however, there is no scientific validation of its usage. Anthelmintic activity of potassium permanganate was tested against parasitic gastrointestinal nematodes in comparison to anthelmintic commercial drugs, Tramisol®, Noromectin® and Valbazen®. There was no egg hatch inhibition induced (<10%) by potassium permanganate at all concentrations as compared to >80% inhibition of commercial drugs, however, 85.24, 98.10 and 90.91% of larval development was induced at 0.5, 1.0 and 1.5 mg/ml, respectively. Larval mortality was observed at 216, 144 and 144 hours at 0.5, 1.0 and 1.5 mg/ml, respectively. The cytotoxicity of this chemical was tested on the brine shrimps and MBDK cells as well. Within 24 hours all the brine shrimps larvae treated with KMnOâ died. A significant decrease in MDBK cell survival was observed at 0.65 mg/ml at 24, 48 and 72 hours. This study has therefore showed that potassium permanganate have anthelmintic activity and concentration dependent cytotoxicity on the mammalian cell lines. In conclusion Cotyledon orbiculata, Hermannia depressa, Nicotiana glauca and potassium permanganate have the potential to supress the aggressiveness of parasitic gastrointestinal nematode and cancer diseases. These substances are therefore potential candidates in treatment of tested pathogens.

There is no abstract available for this thesis.

In May 1953 the first natural history television programme was broadcast from Bristol by naturalist Peter Scott and radio producer Desmond Hawkins. By 1997 the BBC's Natural History Unit has established a global reputation for wildlife films, providing a keystone of the BBC's public service broadcasting charter, playing an important strategic role in television scheduling and occupying a prominent position in a competitive world film market. The BBC's blue-chip natural history programmes regularly bring images of wildlife from all over the globe to British audiences of over 10 million. This thesis traces the changing aesthetics, ethics and economics of natural history film-making at the BBC over this period. It uses archive material, interviews and participant observation to look at how shifting relationships between broadcasting values, scientific and film-making practices are negotiated by individuals within the Unit. Engaging with vocabularies from geography, media studies and science studies, the research contextualises these popular representations of nature within a history of post-war British attitudes to nature and explores the importance of technology, animals and conceptions of the public sphere as additional actors influencing the relationships between nature and culture. This history charts the construction of the actor networks of the Natural History Unit by film-makers and broadcasters as they seek to incorporate and exclude certain practices, technologies and discourses of nature. These networks provide the resources, values and constraints which members of the Unit negotiate to seek representation within the Unit, and present challenges as the Unit seeks to preserve its institutional identity as these networks shift. The thesis tells a series of stories of natural history film-making that reflect one institution's contributions and responses to the contemporary formations of nature, science, the media and modernity.

Brain–specific proteins (BSP) are each relatively specific for particular cell–types within the nervous system. The BSP studied were glial fibrillary acidic protein (GFAP) and S100B for the astrocyte, ferritin for microglia and neurofilaments (Nf) for the axon. BSP are released into the extracellular fluid (ECF) following cellular destruction and during phases of high cellular activity such as astrocytic or microglial activation. ECF BSP equilibrate with those in the cerebrospinal fluid (CSF). This allows us to quantify BSP from the CSF and estimate the overall average of axonal damage (CSF Nf), astrocytic and microglia activation (respectively CSF S100B, CSF ferritin) and astrogliosis (CSF GFAP). New enzyme linked immunoabsorbant assays (ELISA) have been developed for measuring Nf and GFAP in the CSF. Previously established ELISAs have been used to measure S100B and ferritin. It has been shown that spinal cord atrophy in a mouse model of autoimmune encephalomyelitis (EAE) was paralleled by a decrease of Nf indicating loss of axons, and an increase in GFAP indicating astrogliosis. These findings have been confirmed and extended in a human post–mortem study where BSP levels were quantified in multiple sclerosis (MS) lesions of different age and activity. S100B and Nf were associated with acute lesions, ferritin was elevated in all lesion types, while GFAP was increased in both acute and chronic lesions. CSF BSP levels were then quantified in a cross–sectional study of MS patients with the aim of distinguishing clinical subgroups, such as relapsing remitting (RR), primary progressive (PP) and secondary progressive (SP) disease. In addition an attempt was made to relate CSF BSP levels to grades of disability using clinical scales including Kurtzke’s EDSS, an ambulation index (AI) and the 9–hole PEG test (9HPT). It was shown that CSF S100B was higher in RR MS while CSF ferritin was elevated in PP MS patients. The S100B:ferritin ratio emphasised the distinction between the MS subtypes. CSF GFAP was higher in poorly ambulating (AI) and severely disabled (EDSS) patients. CSF GFAP correlated with the EDSS in SP MS patients. This suggests that gliosis is an important feature in SP MS. CSF Nf levels were quantified in a longitudinal study at baseline and at 3–year follow–up. It was shown that more SP/PP than RR MS patients experienced an increase in CSF Nf levels over this time, suggesting cumulative axonal damage in this subgroup. RR MS patients who had elevated CSF Nf levels at baseline had a worse clinical course, suggesting that initial high CSF Nf levels in RR MS patients are a poor prognostic sign. CSF Nf levels at follow–up correlated with the EDSS, AI and 9HPT suggesting that axonal pathology in MS is a dynamic process possibly balancing features of de- and regenerative activities.