published_or_final_version / Physiology / Master / Master of Science

No description available.

Pulmonary arterial tone is regulated in part by the membrane potential (Em) of pulmonary artery smooth muscle cells (PASMCs). The Kv7 family of K+ channels was recently implicated in regulating Em in rat PASMCs and expression of KCNQ1, KCNQ4 and KCNQ5 mRNA, which encode Kv7 channels, was reported. Kv7 activators were beneficial in two-independent mouse models of pulmonary hypertension (PH), which provides further evidence for their role in regulating pulmonary tone. The goals of this study were to: 1) Elucidate the role of Kv7 channels and Em in the hypertensive pulmonary circulation and 2) Study the effects and mechanism of action of a novel Kv7 modulator, zinc pyrithione (ZnPy) on the pulmonary circulation. PH was induced in male Wistar rats by administering a single 60 µg/kg intraperitoneal injection of monocrotaline (MCT). The effects of Kv7 modulators on hypertensive and control pulmonary arteries (PA) were compared using small-vessel myography. The vasoconstrictor effect of the Kv7 blocker, XE991, was enhanced in MCT PA. The Kv7 activators retigabine and ZnPy showed enhanced efficacy in relaxing MCT PA and suppressed raised intrinsic tone identified in MCT PA relative to control PA. The effects of MCT in responses to Kv7 modulators were pulmonary specific as they were not seen in mesenteric arteries from the same animals. Real-time PCR studies revealed that PA from MCT and control rats showed a similar expression of KCNQ1, KCNQ4 and KCNQ5 mRNA transcripts. I propose that the enhanced effects of Kv7 modulators on PA from MCT rats were due to disease-induced depolarization of PASMCs, which raised intrinsic tone and increased Kv7 channel activation at rest. This is the first evidence that Kv7 channels are functional in this model of PH and may serve as potential drug targets. The effects of ZnPy on PASMCs were studied by patch-clamp electrophysiology. ZnPy consistently hyperpolarized PASMCs and significantly increased the K+ current elicited by a voltage-step from -80 to +40 mV. ZnPy also increased the non-inactivating current recorded at 0 mV in some cells. The effects of ZnPy on Em and K+ currents were inhibited by 10 mM tetraethylammonium (TEA) and 1 µM paxilline but not by 50 nM iberiotoxin. XE991 (10µM) inhibited the ZnPy-induced hyperpolarization without altering its effects on K+ currents, suggesting that the current recorded was not responsible for its effect on Em. When tested on intact vessels, ZnPy consistently produced vasodilation. Its effects were unaffected by TEA, paxilline and iberiotoxin; however, XE991 (100 nM) had an inhibitory effect. The results suggest that ZnPy hyperpolarizes PASMCs by activating a TEA, paxilline and XE991 sensitive, but iberiotoxin insensitive channel, most likely a Kv7 channel. Its ability to dilate PA depended on pharmacologically distinct mechanisms, which are unlikely to involve Kv7 channels.

Thesis (M Med(Family Medicine)) -- University of Limpopo, 2010. / BACKGROUND AND OBJECTIVE Tuberculosis remains an important curable disease particularly in the developing world. One third of the world's population is infected with T8 and new infections are occurring at a rate of about one per second(Tuberculosis Wikipedia Encyclopedia 2009).The distribution globally is not uniform with eighty percent of cases in Africa and Asia(Tuberculosis Wikipedia Encyclopedia 2009). Treatment is challenging because it requires compliance to long courses of multiple antibiotics. WHO highlights the global failure of health service providers to deal with the burden of tuberculosis (Fourie et aI1999). The researcher observed that socio-economic factors, political and intrapersonal aspects associated with T8 infection might as well be important to the treatment outcome. It was therefore important to explore factors that could be associated with treatment outcomes in the prison environment where the full impact of these factors could be found. This study was conducted at Potchefstroom prison in North Westprovince of South Africa. METHODS A quantitative cross-sectional study was done. A record review of all T8 patients in Potchefstroom prison who initiated their treatment in 2007 and ending their treatment up to 2010 was conducted. Data was recorded on data collection sheet and results were then analyzed. Descriptive analysis was done to provide frequencies, mean and standard deviation. Measures of association between characteristics and treatment outcome using odds ratio was done. RESULTS 202 T8 patients in this prison had T8 during the period covered by the study. The age group distribution of the patients shows that majority, 142(70.3%) belong to the age group 21- 37 years while those aged 38 - 53 years was 48(23.8%) and their mean age was 33.7yrs. There were 197(97.5%) male and 4(2.0%) female and 1 (0.5%) no records. Of these, therewere 92(45.5%) patients cured 4 (2%) death, 1 (0.5%) treatment failure and 102 recorded as other outcomes belonging to the transferred and treatment interruption cluster. Factors compared with these outcomes were, age, gender, initial body weight, level of education, treatment initiation time, regimen type, social support, co morbidities, smoking, application of DOT ant the type of T8. Factors that were significantly associated with favorable outcomes were occasional visits providing some social support (39.4%, OR 3.78, 95% CI1.25-11.54), DOT application (37.4%, OR 3.99, 95% CI 2.35-11.23), young age (32.6% OR 3.14, 95% CI 2.1-5.3) and Regimen 1 (34.0%, OR 1.5, 95% CI0.11-12.61) Social habits like smoking were significantly higher in patients with other treatment outcome(OR=1.56, 95% CI=1.92 to 2.05), other factors found to be aligned to negative outcomes but lacking statistical significance were extra-pulmonary tuberculosis, non application of DOT, regimens other than regimen 1, and lack of social visits. Factors like co-morbidity and gender were found not to be significantly associated with any treatment outcome because there was no point of difference in the association of different grouping in these categories with particular outcome. CONCLUSION Many factors could be associated with treatment outcomes to some varying degree, but only significant factors explored in this study were considered important. Factors that were ultimately identified as important in determining treatment outcome were age, smoking status, social support, DOT and regimen type. These were factors that were found to be contributory to the pathology of TB in many other studies and which are amenable to interventions that would improve the outcomes.

No description available.

Thesis (M. Sc.)--University of Hong Kong, 1970. / Mimeographed.

Aspergillus species are responsible for a variety of human diseases, ranging from allergic bronchopulmonary aspergillosis to invasive aspergillosis. Identification of Aspergillus species could facilitate the selection of antifungal regimens and epidemiological studies. Most of the clinical microbiology laboratories identify Aspergillus species by traditional phenotypic and/or antigen detection methods, which are laborious, time-consuming and inaccurate. In recent years, sequence analysis of β-tubulin and calmodulin genes becomes widely used for the identification of fungal species due to their relatively high resolving power, universality of usage, and high availability in the public databases. It can also be used for the taxonomic classification and the identification of rare and even novel fungal species. In this study, we aim to evaluate the effectiveness of analyzing the β-tubulin and calmodulin gene sequences for the identification of Aspergillus species and subsequently to determine the clinical spectrum of Aspergillus infections in Hong Kong during 2012-2014. In this study, 48 Aspergillus strains isolated from patients over a 3-year period were characterised to the species level using sequencing of β-tubulin and calmodulin genes and the clinical spectrum of the 48 patients was described. Sequencing of β-tubulin and calmodulin genes showed that all 48 strains were known Aspergillus species. Ten different Aspergillus species were identified, including A. fumigatus (n=16), Aspergillus species of the A. flavus clade (n=7), A. awamori (n=7), A. terreus (n=6), A. tubingensis (n=4), A. sydowii (n=3), A. pseudocaelatus (n=2), A. uniguis (n=1), Aspergillus species of the A. tamarii clade (n=1), and A. austroafricanus (n=1). These Aspergillus species were shown to be associated with respiratory infections, infections of nail, ear canal infections, invasive infections, and eye infection. This study also described the first reported cases of ear infection associated with A. pseudocaelatus. To conclude, sequence analysis of β-tubulin and calmodulin genes enables accurate and rapid Aspergillus species differentiation. / published_or_final_version / Microbiology / Master / Master of Medical Sciences

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

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 1973.