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The importance of the searching for novel antimycobacterial active agents is continually increasing with growing mycobacterial resistance to currently used drugs. However, the resistance-related problems are also associated with other bacteria and fungi. The systematic modification of compounds with a known antimicrobial activity represents one of the possible approaches to overcome this problem. Sulphonamide derivatives may be considered to be such a kind of compounds. That is why we synthesized various sulphathiazole derivatives. Amides were obtained by the reaction of sulphathiazole with appropriate acyl chlorides, substituted ureas from corresponding isocyanates. These ureas were cyclized via oxalyl chloride to form substituted 2,4,5-trioxoimidazolidines. Among derivatives evaluated for their antimycobacterial action, 4-(3- phenethylureido)-N-(thiazol-2-yl)benzenesulphonamide showed the highest activity. Its minimum inhibitory concentrations (MIC) against Mycobacterium tuberculosis My 331/88 (4 µmol/l) were superior to those obtained for sulphathiazole. In the case of nontuberculous mycobacteria (M. avium My 330/88, M. kansasii My 235/88 and M. kansasii My 6509/96), their activities were comparable (≥ 2 µmol/l). Amides showed also a significant antimycobacterial activity, especially against M....

Magister Chirurgiae Dentium (MChD) / Anecdotal and controversial discussion has.always been prompted by the bias of the clinician in relation to whether teeth in the line of fracture should be extracted or retained. In recent years, it became evident to clinicians serving the Maxi 11ofaci aland Oral Surgery Clinic at Groote Schuur Hospital, Cape Town, that a tendency towards reta ining teeth in the 1ine of fractu re did not seem to increase the possi bility of infecti on, providing that circumspection was used. A retrospective analysis of these cases was conducted in order to determine the outcome of our treatment. An independent sample of the 151 patients were investigated in relation to age, sex predilection, the effect timing has on the outcome of treatment and the incidence of infection when teeth in the line of mandibular fracture were extracted or retained. The results of this study has shown that most of our patients were young (aged 20-29yrs) and therefore a tendency to retain teeth was found. In older patients, (aged 30-49yrs), the tendency was to extract teeth. Males presented more than females in a 3:1 ratio. Patients treated early « 24hrs) had most of their teeth retained while others treated after 7 days had their teeth extracted. The infecti on rate was 2 percent if teeth were retained and 5 percent if teeth were extracted. A1though the difference was not statistically significant, it appeared that the retenti on of teeth in the 1ine of fracture presented more advantages to both patient and clinician.

Before the availability of antibiotics minor infections could become life threatening. Nurses working in voluntary and public hospitals in Britain were exposed to such risks. This thesis uses both oral testimonies and published sources in order to examine their practices concerning the management of infection risks. The detail of nursing work in this period has been generally hidden in nursing histories of the 1930s and 1940s which have addressed mainly political, recruitment, educational, registration and status issues. Whilst these histories may comment about menial duties, and the culture and discipline in clinical areas, they lack detailed exploration of the day-to-day work of the nurse. This novel study contributes to redressing the balance by examining nursing practice between the discovery of penicillin in 1929 and its widespread availability in Britain in 1948. Data analysis, including the oral testimonies of nineteen former nurses who worked between 1929 and 1948, suggests that nursing practice during this period placed enormous emphasis on cleanliness and hygiene. It is argued that this was linked to sanitarianism which influenced nursing practice before its replacement by germ theory. Probationer nurses learnt their skills in managing infection risks to themselves and their patients in a disciplined and safe way. This was achieved through the exercise of strict routines and a hierarchy of tasks that provided a graduated exposure to the patient and infection risks. This thesis draws on debates in the literature about purity, vocation and status to explore, and add weight to this argument. The analysis also identifies that the introduction of sulphonamide drugs and antibiotics altered nursing practices in the management of both infection risks and patients with infection. Whilst the full effects of these changes are not examined in this thesis, it is argued that the significant impact of these drugs was such that the emphasis on cleaning and hygiene became diminished in importance and nursing had to redefine its role. It suggests that more prominence needs to be given to changes in clinical practice in the history of nursing. This study breaks new ground by suggesting the rigorous training of nurses in cleaning and hygiene tasks was needed in order to manage the infection risks faced by nurses before the availability of antibiotics.

<p>Extensive use of the sulphonamide drugs against the bacterium <i>Neisseria meningitidis</i> has resulted in drug resistance development. Sulphonamide resistance in <i>N. meningitidis</i> is caused by alterations in the chromosomal <i>folP</i> gene, coding for DHPS (dihydropteroate synthase). One type of resistant DHPS has high sequence divergence compared to DHPS from susceptible strains. This divergent DHPS has a duplication of two amino acids, crucial for resistance, and an altered amino acid in position 68, important for both resistance and substrate binding. When introduced into a susceptible DHPS, these two alterations did not incur resistance and resulted in abnormal substrate binding properties. This indicated that the divergent DHPS was not directly developed by mutations, but rather had been acquired by horizontal transfer of <i>folP</i> from another species.</p><p>Commensal <i>Neisseria</i> species are implied as the origin of the horizontally transferred resistance. Sulphonamide-resistant commensal <i>Neisseria</i> isolates were detected in throat swabs from healthy individuals not exposed to these drugs; however, transformation of resistance from these commensals to <i>N. meningitidis</i> was restricted in the laboratory. A comparison of the genomic region surrounding <i>folP</i> revealed differences in gene organisation and in the DNA uptake sequence between <i>N. meningitidis</i> and distantly related commensals. These differences are likely to restrict transformation between distantly related <i>Neisseria</i> species.</p><p>DHPS participates in the folate biosynthesis pathway. The enzyme preceding DHPS in the pathway, HPPK (hydroxymethyl-dihydropterin pyrophosphokinase), from <i>N. meningitidis</i> was characterised and a method for studying substrate channelling from HPPK to DHPS was developed. The information gained could be exploited in the search for new antibiotics.</p><p>In conclusion, well-adapted sulphonamide-resistant strains of <i>N. meningitidis</i> and commensal <i>Neisseria</i> are established in the bacterial population and resistance can be horizontally spread by natural transformation. This may explain the abundance of sulphonamide-resistant <i>N. meningitidis</i>, although these drugs are no longer used against this bacterium.</p>

Extensive use of the sulphonamide drugs against the bacterium Neisseria meningitidis has resulted in drug resistance development. Sulphonamide resistance in N. meningitidis is caused by alterations in the chromosomal folP gene, coding for DHPS (dihydropteroate synthase). One type of resistant DHPS has high sequence divergence compared to DHPS from susceptible strains. This divergent DHPS has a duplication of two amino acids, crucial for resistance, and an altered amino acid in position 68, important for both resistance and substrate binding. When introduced into a susceptible DHPS, these two alterations did not incur resistance and resulted in abnormal substrate binding properties. This indicated that the divergent DHPS was not directly developed by mutations, but rather had been acquired by horizontal transfer of folP from another species. Commensal Neisseria species are implied as the origin of the horizontally transferred resistance. Sulphonamide-resistant commensal Neisseria isolates were detected in throat swabs from healthy individuals not exposed to these drugs; however, transformation of resistance from these commensals to N. meningitidis was restricted in the laboratory. A comparison of the genomic region surrounding folP revealed differences in gene organisation and in the DNA uptake sequence between N. meningitidis and distantly related commensals. These differences are likely to restrict transformation between distantly related Neisseria species. DHPS participates in the folate biosynthesis pathway. The enzyme preceding DHPS in the pathway, HPPK (hydroxymethyl-dihydropterin pyrophosphokinase), from N. meningitidis was characterised and a method for studying substrate channelling from HPPK to DHPS was developed. The information gained could be exploited in the search for new antibiotics. In conclusion, well-adapted sulphonamide-resistant strains of N. meningitidis and commensal Neisseria are established in the bacterial population and resistance can be horizontally spread by natural transformation. This may explain the abundance of sulphonamide-resistant N. meningitidis, although these drugs are no longer used against this bacterium.

The most important substances of the group of perfluorinated compounds are perfluorooctyl sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluorooctane sulphonamide (FOSA). Perfluorinated compounds have special physical and chemical properties, which make them valuable for usage in different industrial branches. These properties, which make them so useful are also the reason, why they are so harmful for the environment. The target of theoretical part of the diploma thesis was processing of literature searche on the topic: Evaluation of environmental load by perfluorinated compounds. In the experimental part was developed and optimized a method that was used for the identification and quantification of selected pollutants contained in real soil samples.