The variation of Arginine kinase (Ark) genotype frequency among populations of Thais clavigera has been reported in previous study. However, the difference which is originated from self-seeding or differential selection after recruitment is not understood. To answer this question, the spatial (i.e. Shainsan, Taisi, Budai, and Chiku) and temporal (sell length: <15mm, 15-20mm, 20-30mm, 30-40mm, and >40mm; year: 2001 and 2003) variations of Ark allozyme were examined by starch gel electrophoresis. There was no significant difference in the ratio of Ark genotypes (ark63/63, ark63/100, ark100/100) in the size range of <15mm among Shainsan, Taisi and Chiku. The result indicated that the populations of T. clavigera is from the same recruitment. In the size range of 15-20mm, the frequency of ark63/63 increased from southern to northern populations, i.e. 0.21(Chiku) < 0.33(Budai) < 0.60(Taisi) < 0.66(Shainsan), respectively. It is proposed that the variation of Ark genotypes among populations is resulting from stress of temperature or dessication. A significant difference in the ratio of Ark genotypes was found in the population of Taisi with the size range of 30-40mm. Besides, the frequency of Ark genotypes among populations was not related to the degree of imposex.

The genetic structure of oyster drill Thais clavigera along the west coast of Taiwan were assayed by starch gel electrophoresis. Factors of locality¡]i.e. Shainsan, Taisi, Budai, Chiku¡^,maturity¡]i.e. mature, immature¡^ and sampling time¡]i.e.1999.7~2000.3, 2000.11¡^ were analyzed to evaluate their effect on drill¡¥s genetic structure . Four of the eleven investigated enzyme loci were polymorphic , i.e. Ark, Lap-1, Lap-2, and Pgm-1. Among the four populations , the mean heterozygosity¡]H¡^and genetic distances¡]D¡^ ranged from 0.100 to 0.129 and from 0.0005 to 0.0029, respectively. Therefore, T. clavigera along the west coast of Taiwan belongs to the same population. However, differentiation among populations still existed which was contributed by Ark locus. According to the degree of differentiation, the four populations were ranked as Shainsan¡BBudai¡BTaisi and Chiku . A similar trend was also observed in the four populations, as the drill size increased, the mean heterozygosity and the heterozygosity of Ark locus increased. Sampling time had no significant effect on genetic structure of populations. It is suggested that environmental factors¡]e.g. environmental quality and topography¡^and drill¡¦s reproductive ecology may be important in determining the genetic structure of populations.

The ability of an animal to respond and adapt to stimuli is necessary for its survival and involves plasticity and coordination of multiple levels of biological organization, including behavior, tissue organization, hormones, and gene expression. Each of these levels of response is complex, and none of them responds to stimuli in isolation. Thus, to understand how each system responds, it is necessary to consider its role in the context of the entire organism. Here, I have used the African cichlid fish Astatotilapia burtoni and its extraordinary phenotypic plasticity to investigate how animals respond to a change in social status from subordinate to dominant and attempted to integrate these multiple levels of biological response, as well as the roles of several candidate neuromodulators,. First, I have described how male A. burtoni become more aggressive and reproductive during their transition to dominance as well as increasing circulating levels of testosterone and estradiol and the histological organization of their testes. I then mapped the distribution of expression of two behaviorally relevant neuropeptides, arginine vasotocin and isotocin, and their respective receptors, throughout the A. burtoni brain, and found that they were highly expressed in several brain areas important for social behavior and decision-making. I then investigated the role of arginine vasotocin in social status and behavior via pharmacological manipulation and qPCR, showing the importance of arginine vasotocin in controlling the transition to dominance. Lastly, I investigated the role of aromatase, testosterone, and estradiol in male A. burtoni, both in stable dominant males and in males as they transition to dominance, using pharmacological manipulation and quantitative radioactive in situ hybridization, illustrating that estradiol synthesis during dominance is dependent on aromatase activity and necessary for aggressive behavior. / text

Aims There is a high prevalence of hypertension in the African population and it is known that vascular dysfunction (including nitric oxide (NO) bio-availability markers) play an important role in the development of cardiovascular diseases. Since very little is known regarding the role of markers of NO bio-availability in Africans, the aim of this study was to compare markers of NO bio-availability (namely L-arginine, L-citrulline, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA)), ambulatory blood pressure (BP) and markers of end organ damage between African and Caucasian school teachers. Additionally, we also aimed to determine whether these markers of NO bio-availability are associated with ambulatory BP and markers of end organ damage in both ethnic groups. Methods The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study was a cross-sectional study, including urbanised African (N=181) and Caucasian (N=209) men and women, between the ages of 25 and 65 years. Cardiovascular measurements included ambulatory blood pressure, pulse wave velocity (PWV), electrocardiographic Cornell product and carotid intima media thickness (cIMT). Anthropometric measurements included height, weight and waist circumference. Various bio-markers were analysed, including glucose, L-arginine, ADMA, SDMA, Lcitrulline, reactive oxygen species, albumin-to-creatinine ratio (ACR) and estimated creatinine clearance (eCCR). Characteristics of groups were compared with independent T-tests and Chi-square tests. Single and partial analyses were used to investigate associations between NO bioavailability markers with ambulatory BP measurements and markers of end organ damage. Analyses of covariance (ANCOVA) were used for comparison of variables between groups to determine significant differences, while adjusting for age, body mass index and antihypertensive medication. Forward stepwise multiple regression analyses were performed to determine if independent associations exist between ambulatory BP measurements or markers of end organ damage with either- L-arginine, L-citrulline, ADMA or SDMA as the main independent variable. Results and conclusion The Africans and Caucasians were of similar ages. However, the Africans had higher blood pressure therefore their cardiovascular profile was unfavourable compared to that of the Caucasians. The inhibitors of NO biosynthesis, ADMA and SDMA, were significantly lower in the Africans (p=0.046; p<0.001, respectively). However, the NO bio-availability markers, L-arginine and L-citrulline, were higher in the African compared to the Caucasian participants (all p values <0.05) regarded as significant. When performing unadjusted analyses, we found significant negative associations between eCCR and L-citrulline in all four subgroups: African men (r=-0.27; p=0.013), African women (r=-0.24; p=0.021), Caucasian men (r=-0.21; p=0.044) and Caucasian women (r=-0.28; p=0.003). The association of eCCR with L-citrulline was confirmed to be independent of confounders in all groups: African men (R2=0.46; β=-0.23; p=0.006), African women (R2=0.68; β= -0.12; p=0.046), Caucasian men (R2=0.62; β= -0.24; p<0.001) and Caucasian women (R2=0.72; β= -0.13; p=0.029). This implicates that renal function may be detrimentally affected by L-citrulline concentrations. In the Caucasian men and women negative correlations between eCCR and SDMA were found before adjustments (r=-0.33; p=0.003 and r=-0.26; p=0.006, respectively). This phenomenon was confirmed in the forward stepwise multiple regression analysis in Caucasian men (R2=0.75; β= -0.27; p<0.001) and women (R2=0.73; β= -0.21; p<0.001), while no associations were found in the Africans. This result is not unexpected, since SDMA can only be eliminated by the kidneys and is therefore an important risk marker for the early detection of renal dysfunction. In Caucasian men we found that ADMA correlated with ACR (r=0.36; p=0.001), night-time SBP (r=0.34; p=0.002) and night-time DBP (r=0.25; p=0.023) with single linear regression analyses. A similar trend was shown in African men with night-time SBP (r= 0.20; p=0.089) and night-time DBP (r= 0.21; p=0.078) respectively, but this association was absent in the Caucasian and African women. After adjustments for age and body mass index, the associations with ADMA, ACR and SBP in the Caucasian men remained. However, a negative association between eCCR and ADMA also became evident in the African men (r=- 0.24; p=0.025) and remained significant in the forward stepwise multiple regression analysis (R2=0.44; β= -0.18; p=0.034). It is, however, not clear why our results were gender specific, but we could speculate that the female sex hormones may play a part in protecting the vascular endothelium. Apart from the associations described above, there were no significant independent associations between the markers of the NO cycle (such as L-arginine) and PWV, cIMT, eCCR, ACR or Cornell product. In conclusion, although Africans presented a more vulnerable cardiovascular profile, we found a consistent negative association between renal function and L-citrulline in all participants, which has only been reported previously in patients with chronic renal disease. Additionally we found a gender-specific link between renal function and ADMA in African and Caucasian men. Our results may indicate that in the general population, markers of NO bioavailability may be associated with early changes in renal function, accompanying elevated blood pressure. / Thesis (MSc (Physiology))--North-West University, Potchefstroom Campus, 2013

Aims There is a high prevalence of hypertension in the African population and it is known that vascular dysfunction (including nitric oxide (NO) bio-availability markers) play an important role in the development of cardiovascular diseases. Since very little is known regarding the role of markers of NO bio-availability in Africans, the aim of this study was to compare markers of NO bio-availability (namely L-arginine, L-citrulline, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA)), ambulatory blood pressure (BP) and markers of end organ damage between African and Caucasian school teachers. Additionally, we also aimed to determine whether these markers of NO bio-availability are associated with ambulatory BP and markers of end organ damage in both ethnic groups. Methods The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study was a cross-sectional study, including urbanised African (N=181) and Caucasian (N=209) men and women, between the ages of 25 and 65 years. Cardiovascular measurements included ambulatory blood pressure, pulse wave velocity (PWV), electrocardiographic Cornell product and carotid intima media thickness (cIMT). Anthropometric measurements included height, weight and waist circumference. Various bio-markers were analysed, including glucose, L-arginine, ADMA, SDMA, Lcitrulline, reactive oxygen species, albumin-to-creatinine ratio (ACR) and estimated creatinine clearance (eCCR). Characteristics of groups were compared with independent T-tests and Chi-square tests. Single and partial analyses were used to investigate associations between NO bioavailability markers with ambulatory BP measurements and markers of end organ damage. Analyses of covariance (ANCOVA) were used for comparison of variables between groups to determine significant differences, while adjusting for age, body mass index and antihypertensive medication. Forward stepwise multiple regression analyses were performed to determine if independent associations exist between ambulatory BP measurements or markers of end organ damage with either- L-arginine, L-citrulline, ADMA or SDMA as the main independent variable. Results and conclusion The Africans and Caucasians were of similar ages. However, the Africans had higher blood pressure therefore their cardiovascular profile was unfavourable compared to that of the Caucasians. The inhibitors of NO biosynthesis, ADMA and SDMA, were significantly lower in the Africans (p=0.046; p<0.001, respectively). However, the NO bio-availability markers, L-arginine and L-citrulline, were higher in the African compared to the Caucasian participants (all p values <0.05) regarded as significant. When performing unadjusted analyses, we found significant negative associations between eCCR and L-citrulline in all four subgroups: African men (r=-0.27; p=0.013), African women (r=-0.24; p=0.021), Caucasian men (r=-0.21; p=0.044) and Caucasian women (r=-0.28; p=0.003). The association of eCCR with L-citrulline was confirmed to be independent of confounders in all groups: African men (R2=0.46; β=-0.23; p=0.006), African women (R2=0.68; β= -0.12; p=0.046), Caucasian men (R2=0.62; β= -0.24; p<0.001) and Caucasian women (R2=0.72; β= -0.13; p=0.029). This implicates that renal function may be detrimentally affected by L-citrulline concentrations. In the Caucasian men and women negative correlations between eCCR and SDMA were found before adjustments (r=-0.33; p=0.003 and r=-0.26; p=0.006, respectively). This phenomenon was confirmed in the forward stepwise multiple regression analysis in Caucasian men (R2=0.75; β= -0.27; p<0.001) and women (R2=0.73; β= -0.21; p<0.001), while no associations were found in the Africans. This result is not unexpected, since SDMA can only be eliminated by the kidneys and is therefore an important risk marker for the early detection of renal dysfunction. In Caucasian men we found that ADMA correlated with ACR (r=0.36; p=0.001), night-time SBP (r=0.34; p=0.002) and night-time DBP (r=0.25; p=0.023) with single linear regression analyses. A similar trend was shown in African men with night-time SBP (r= 0.20; p=0.089) and night-time DBP (r= 0.21; p=0.078) respectively, but this association was absent in the Caucasian and African women. After adjustments for age and body mass index, the associations with ADMA, ACR and SBP in the Caucasian men remained. However, a negative association between eCCR and ADMA also became evident in the African men (r=- 0.24; p=0.025) and remained significant in the forward stepwise multiple regression analysis (R2=0.44; β= -0.18; p=0.034). It is, however, not clear why our results were gender specific, but we could speculate that the female sex hormones may play a part in protecting the vascular endothelium. Apart from the associations described above, there were no significant independent associations between the markers of the NO cycle (such as L-arginine) and PWV, cIMT, eCCR, ACR or Cornell product. In conclusion, although Africans presented a more vulnerable cardiovascular profile, we found a consistent negative association between renal function and L-citrulline in all participants, which has only been reported previously in patients with chronic renal disease. Additionally we found a gender-specific link between renal function and ADMA in African and Caucasian men. Our results may indicate that in the general population, markers of NO bioavailability may be associated with early changes in renal function, accompanying elevated blood pressure. / Thesis (MSc (Physiology))--North-West University, Potchefstroom Campus, 2013

Ellipticine (EPT), a natural plant polyphenolic compound, has long been known for its significant anticancer and anti-HIV activities. Recent study on its photophysical properties has revealed that ellipticine has three molecular states: protonated, neutral and crystalline. Further in vitro cytotoxicity tests indicated that protonated ellipticine exhibited much higher anticancer activity than the other two states. To maximize drug therapeutic effect, a small library of ariginine-rich ionic complementary peptides derived from EAK, including EAR8-II, EAR8-a, ELR8-a, and EAR16-II, were investigated as a potential carrier to deliver prescribed protonated ellipticine for treatment of cancer. Fluorescence study demonstrated that all four peptides were able to solubilize and stabilize protonated ellipticine in aqueous solution at 5:1 mass ratio of peptide-to-ellipticine (0.5: 0.1 mg/mL) even upon 4000 times dilution. Physicochemical characteristics of peptides self-assemblies and peptide-ellipticine complexes such as particle size, surface charge, secondary structure and morphology were determined by dynamic light scattering (DLS), zeta potential, circular dichroism (CD) , atomic force microscopy (AFM) and transmission electron microscopy (TEM), respectively. Then the ellipticine maximum suspension was determined by ellipticine UV-absorption. With the help of the peptides and mechanical stirring overtime, up to 100% ellipticine could be uptaken and stabilized in the solution as protonated ellipticine. In vitro cytotoxicity tests indicated that the peptides were demonstrating significant biocompatibility without affecting the survival of two cancer cell lines, human lung carcinoma cell line A549 and breast cancer cell line MCF-7, whereas the complexes with protonated ellipticine were found to show great anticancer activity to the two cancer cell lines. The IC50 values were obtained for each of four different peptide-ellipticine complexes ranged from 0.36±0.12 to 18.90±0.46 μM. It is worth noting that the IC50 value of EAR16-ellipticine complex to MCF-7 was over 50 times higher than that one to A549, which presented that EAR16-ellipticine complex has a selective targeting activity to A549, with the lowest IC50 value of 0.36±0.12 μM among all four complexes. Such a result indicated that this library of novel arginine-rich ionic complementary peptides had a great potential to encapsulate prescribed protonated ellipticine and exhibited an excellent anticancer activity upon serial dilution in aqueous solution. Overall, the charge distribution and increased hydrophobicity of the short (8 amino acids length) peptides seemed not to affect the complex formation and its therapeutic efficacy in vitro; however, the increase in length of the peptides significantly altered the nanostructure of peptides and its complexation with ellipticine, increased the therapeutic efficacy of EAR16-EPT to A549. This work provides essential information for peptide sequence design in the development of self-assembling peptide-based delivery of hydrophobic anticancer drugs.

The aim of this study was to investigate in vitro transdermal diffusion of a small peptide namely arginine vasopressin (AVP) with the aid of the novel PheroidTM drug delivery system. Generally, peptides seem unfit for transdermal permeation, but it was thought prudent to explore the suitability of this lipid-based system after success was achieved with entrapment of tuberculostatics, bacteria and viruses. Bestatin (a selective aminopeptidase inhibitor) was employed to circumvent any skin-related degradation of the active. Therefore, the effect of bestatin on the preservation of AVP during diffusion was investigated. Vertical Franz cell diffusion studies were conducted with female abdominal skin, with AVP at a concentration of 150 pglml in the donor phase and Hepes buffer as the receptor phase over a twelve-hour period. To prove entrapment of AVP within the lipid structures of the PheroidsTM, fluorescentlylabelled samples were monitored by means of confocal laser scanning microscopy (CLSM), which revealed definite entrapment. In vitro permeation profiles for AVP exhibited a biphasic character, with the majority of permeation occurring during the first two hours. The PheroidTM delivery system proved to be advantageous when applied as delivery medium. The inclusion of bestatin has an enhancing effect on permeation probably due to its protection of AVP. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Thesis (Ph.D.)--Tufts University, 2003. / Adviser: L. Michael Romero. Submitted to the Dept. of Biology. Includes bibliographical references (leaves 158-180). Access restricted to members of the Tufts University community. Also available via the World Wide Web;

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Nöroloji Anabilim Dalı, 2006. / Bibliyografya var.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2007. / Härtill 4 uppsatser.