Association of gene polymorphisms of aldosterone synthase and angiotensin converting enzyme in pre-eclamptic South African Black women.

INTRODUCTION: The exact cause of preeclampsia (PE) remains elusive. Recently, many researchers have focused on the role of genetic variations in pathogenesis of PE. The renin-angiotensin-aldosterone system is affected in the pathogenesis of PE. OBJECTIVES: To determine association of gene polymorphisms of aldosterone synthase (CYP11B2) and angiotensin converting enzyme (ACE) in PE and normotensive South African Black women. METHODS: A group of 603 South African Black pregnant women, 246 normotensive and 357 with PE, was recruited. Purified DNA was extracted from venous blood. The distribution and frequencies of gene polymorphisms of CYP11B2 (C-344T) and ACE deletion/insertion (D/I) were determined by real time polymerase chain reaction. RESULTS: As the main outcome measure, the risk of C allele for PE was 1.28 (95%CI: 0.94-1.74; p = .1) for all allele comparisons. Thus no significant association with development of PE was observed for the CYP11B2 variants. However, post analysis of the distribution of TT genotypes of CYP11B2 were higher in the HIV uninfected normotensive than in the HIV uninfected PE group (OR: 0.47, 95%CI: 0.27-0.79, p = .0027). The C alleles of late-onset PE and HIV uninfected PE were higher than all normotensive and HIV uninfected normotensive (OR: 1.47, 95%CI: 1.02-2.10, p = .03 and OR: 1.77, 95%CI: 1.13-2.81, p = .0094 respectively). The CT genotype of CYP11B2 was statistically significant between normotensive and PE in HIV uninfected groups (OR: 2.24, 95%CI: 1.28-3.98, p = .0026). There was no significant difference in frequencies of D/I for ACE gene in PE.

The effects of sildenafil citrate on urinary podocin and nephrin mRNA expression in an L-NAME model of pre-eclampsia.

We investigated the effects of sildenafil citrate (SC) on podocyturia in N ω-nitro-L-arginine methyl ester hydrochloride (L-NAME) model of pre-eclampsia (PE). One hundred and twenty Sprague-Dawley rats (SDR) were divided into five groups like pregnant control (PC), early-onset PE (EOPE), late-onset PE(LOPE), early and late-onset PE with SC-treated groups [EOPE (SC); LOPE (SC)]. PE was induced in SDR by oral administration of L-NAME in drinking water for 4-8 days for EOPE and 8-14 day for LOPE. The blood pressure, urine volume and total urine protein were increased in EOPE and LOPE groups when compared to PC, and all the above parameters decreased in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The EOPE and LOPE groups showed an increase in urinary nephrin mRNA and podocin mRNA levels compared to PC group. Increases in serum and renal soluble fms-like tyrosine kinase-1 (sFlt-1) expression levels and decreases in renal vascular endothelial growth factor (VEGF) expression and serum placenta growth factor (PlGF) levels were observed in EOPE and LOPE groups when compared to PC group. In addition, decreases in serum and renal sFlt-1 expression levels and increases in renal VEGF expression and serum PlGF levels were observed in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The light microscopy showed that the renal tissue of L-NAME-treated rats had extensive glomerular damage, tubular damage and infiltration by mononuclear cells when compared to PC group. Therefore, SC ameliorated podocyturia through its effects on the antiangiogenic/angiogenic status in this animal model.

The effects of sildenafil citrate on uterine angiogenic status and serum inflammatory markers in an L-NAME rat model of pre-eclampsia.

Pre-eclampsia (PE), a hypertensive disorder of pregnancy, is detrimental to both mother and foetus. There is currently no effective treatment, but we have shown that Sildenafil Citrate (SC) improve various foetal outcomes in Nω-nitro-L arginine methyl ester (L-NAME) rat model of PE. Therefore, we aimed to investigate the effects of SC on a uterine angiogenic status and serum inflammatory markers in an L-NAME rat model of PE. One hundred and twenty adult nulliparous pregnant female Sprague-Dawley rats were used for the study. These were divided into five equal groups; the pregnant control, early and late onset PE and respective SC treated animals. Hypertension was manifested by considerably increased systolic blood pressure and placental lipid peroxidative marker (thiobarbituric acid reactive substances) and also we assessed the activities of plasma nitric oxide level, serum inflammatory marker (TGF-ß and IFN-γ) and uterine angiogenic status (VEGF and sFlt-1) at two stages of PE. The administration of SC decreased systolic blood pressure, placental lipid peroxidation product and altered uterine angiogenic status; increased plasma nitric oxide levels in an early and late onset L-NAME model of PE. In addition, histological findings of SC treated preeclamptic rat placenta support the biochemical findings of this study. Our findings revealed that SC enhanced plasma NO levels and uterine angiogenic status in an L-NAME model of PE at two gestational stages.

High prevalence of cardiovascular risk factors in Durban South African Indians: The Phoenix Lifestyle Project.

BACKGROUND: Previous studies show a high prevalence of cardiovascular (CV) risk factors in South African (SA) Asian Indians, with the emergence of premature coronary artery disease in young Indian subjects. OBJECTIVE: To determine the prevalence of CV risk factors in this population. METHODS: This was a cross-sectional study of randomly selected adults aged 15 - 64 years from the suburb of Phoenix in Durban, KwaZulu-Natal Province, SA. All participants had demographic, anthropometric and biochemical measurements using the modified World Health Organization (WHO) STEPwise survey methods. Hypertension, obesity, lipid abnormalities and diabetes mellitus (DM) were diagnosed using WHO criteria. Age-standardised frequencies for glycaemic indices were calculated according to the WHO standard world population distribution. RESULTS: Of the 1 428 subjects who responded (response rate 72.1%), complete data for analysis were available on 1 378 (1 001 women). The mean age was 45.5 (standard deviation 13) years. There were high prevalences of hypertension (47.5%), DM (20.1%), total body obesity (raised body mass index) (32.4%) and increased waist circumference (73.1%). The 'thin-fat' Asian phenotype (isolated abdominal obesity) was found in only 4.8% of participants. High prevalences of total body obesity (32.1%), increased waist circumference (31.3%) and insulin resistance (28.2%) were documented in the youngest age group. Over half of the males and 14.6% of females were current smokers. Diabetic dyslipidaemia was found in 61 subjects (4.4%). In multivariate analysis, age, triglycerides and waist circumference measurement were significant independent risk factors associated with DM and, together with fasting glucose, also predicted hypertension. CONCLUSION: Compared with Asian Indian subjects with similar environmental exposure in previous studies, the magnitude of change in risk factor prevalence over the past two decades has been of epidemic proportions.

The optimization of a chronic nitric oxide synthase (NOS) inhibition model of pre-eclampsia by evaluating physiological changes.

OBJECTIVES: In order to address the gap in our understanding of the pathogenesis and pathophysiology of PE, we optimized the NOS inhibition animal model by comparing changes in different parameters at various time frames during pregnancy, in both early and late-onset PE. STUDY DESIGN: 120 nulliparous Sprague-Dawley rats were divided into 5 groups (n=24). A pregnant control, two groups that represented early and late-onset PE and two groups that were treated with sildenafil citrate (SC) to show reversal of the pre-eclamptic-like symptoms. RESULTS: Our results showed that treatment with L-NAME caused significant changes in physiological parameters for both early and late-onset PE groups. There was a significant increase in systolic blood pressure (SBP) levels in the early-onset PE group (128.5±5.71 mmHg) and late-onset PE group (128.3±6.15 mmHg) on day 19 compared to the SBPs on day 0, (p<0.01). Urine excretion volumes in the early-onset PE group (13.62±3.18 mL) and in the late-onset PE (13.28±2.60 mL), compared to the pregnant control group (11.96±1.9 mL) were also increased (p<0.05). There was also an increase in total urinary protein in the early-onset PE group (0.62±0.08 g/L and the late-onset PE group (0.45±0.05 g/L), when compared to the pregnant control group (0.38±0.07) (p<0.05). We also found a decrease in fetal numbers in the PE group in comparison to the pregnant control and SC treated groups. The remission of these signs was seen after delivery of the fetuses. We also demonstrated that treatment of this syndrome with SC prevented the development of these signs. CONCLUSIONS: The NOS inhibition model can be used for the study of the pathogenesis and pathophysiology of PE, since the pathogenic changes mimic those of early and late-PE.

Medicine and medical sciences in Africa.

The year 2014 is an important year because it will mark the 25th Anniversary of the founding of the African Association of Physiological Sciences (AAPS) and initial talks to launch the International Society for Pathophysiology (ISP). Both these organizations had a foothold in Finland and both occurred during the IUPS Centennial Celebration Congress in 1989. The congress was hosted by the Finnish Physiological Society in Helsinki, Finland in July 1989. For both organizations, Prof OsmoHänninen was instrumental in the launching and inauguration of AAPS and also to initiate the creation of ISP. In order to celebrate the 25th Anniversaries of both organizations it was decided to hold the ISP2014 congress on the African soil. Hence in 2004, at the 4th international congress of AAPS held in Morocco, Wail Benjeloun.the then secretary general of AAPS, submitted successfully a bid to host ISP2014 in Morocco. Following the inauguration of AAPS in Helsinki, the 1st Congress of AAPS was held in Nairobi, Kenya in 1992 where the Constitution of AAPS was drawn up. The Constitution was adopted at the 2nd congress of AAPS in Durban, South Africa in 1997. Following this congress, the next congress, as scheduled, was held in Pretoria, South Africa in 2000. The last congress (6th) of AAPS was held on 1-5 September 2012 in Ismailia, Egypt. This was an historical congress because of many reasons and amongst these was the appointment of Anthony B. Ebeigbe, Department of Physiology, University of Benin, Nigeria as its first Editor-in-Chief of its official journal, the Journal of the African association of Physiological Sciences (JAAPS). He successfully published the first issue in June 2013, as mandated in Ismailia. The World's medicine has its initial root in Africa and in fact it was in Memphis, Egypt as early as 2700 BC. During the Ptulomaic period the seat of medicine was in Alexandria, Egypt and Medical knowledge then spread to the Greeks 330 BC. Many western medical scientists acknowledge learning medicine and anatomy form the Egyptian experts. The University of Al Karaouine, in Fez, Morocco, Africa is considered the oldest continuously operating university in the world and has been a center of learning for more than 1,000 years. Medicine in Africa has been acknowledged by many authoritarians to be well developed, long before its development in Greece and other European Countries. Almost every African country has medical and medical sciences societies and associations. According the WHO, African journals online (AJOL) as the worlds largest collection of peer-reviewed journals. It is also believed that Africa will play a major role in Sciences in the future, and in fact one of the Worlds leading palaeo-anthropologist was a South African.

The role of angiogenic, anti-angiogenic and vasoactive factors in pre-eclamptic African women: early- versus late-onset pre-eclampsia.

The pathogenesis and aetiology of pre-eclampsia (PE) is still unclear. We investigated the role of angiogenic, antiangiogenic and vasoactive factors in black South African women with early- and late-onset PE. Serum soluble fms-like tyrosine kinase 1 (sFlt-1), soluble vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) levels were determined using the ELISA technique, and placental mRNA expression levels of sFlt-1, VEGF, PlGF and AT1 receptors were determined using real-time PCR. Serum sFlt-1 levels were significantly elevated and PlGF significantly reduced in early-onset PE compared to the normotensive group. Placental VEGF mRNA expression levels were significantly reduced in the late-onset preeclamptic group compared with the normotensives. The placental mRNA expression of AT1 receptor in the late-onset pre-eclamptic group was relatively raised compared to the normotensives, suggesting hypersensitivity to pressor agents. We believe that the excess of serum sFlt-1 and reduced VEGF and PlGF levels favour an anti-angiogenic state and endothelial dysfunction leading to PE, and that the aetiology and pathogenesis of early- and late-onset PE differ.

Effects of a unique electromagnetic field system on the fertility of rats.

The authors investigated the fertility of male and female rats exposed to a unique-design electromagnetic apparatus (Hivex Electromagnetic Field System-5 [EMFS-5]), which establishes an omni-directional, spatial field and has a wide band range of 100 MHz-3 GHz. We used 32 male and 32 female rats that were proven breeders. Sixteen rats from each sex were exposed to the EMFS for 8h/day for 10 days. The others were sham exposed. The rats were divided into the following 4 groups: in group AG1-AG8, males and females were exposed; in group AG9-AG16, only females were exposed; in group AG17-AG24, only males were exposed; and in group AG25-AG32, males and females were sham exposed. After exposure for each group, a male rat was cohabited with a female rat until parturition. The authors' results showed that except for 1 male, the fertility of all other rats was not affected. They did not see differences in reproductive ability (latency to parturition, litter size, number of male/female pups, male-to-female ratio, mass of pups at weaning) between experimental groups and the sham exposed group. The authors concluded that exposure of male and female rats to the Hivex EMFS-5 does not affect fertility or reproductive ability.

Medical practitioners' reactions towards family medicine as a speciality in South Africa

Background: Family physicians are trained to treat a wide range of diseases; treatment being centred on the patient; family and community irrespective of age; gender; or ethnic or racial background. To deal with inequalities in health care; the South African government introduced the concept of a district health system in 1997. It was only in August 2007; however; that family medicine was legislated as a speciality. This study was undertaken prior to the enactment of this legislation. Methods: A descriptive quantitative study using a self-administered questionnaire was undertaken. A convenience sampling technique was used (N = 60) to assess the reactions of medical practitioners towards the impending legislation. Results: Overall; 60of the sample was in favour of the legislation. There were no significant differences between those working in the private and public sectors or between generalists and specialists. With regard to those not in favour of the legislation compared to those in favour of the legislation; a significantly increased number answered the following statements in the affirmative: (i) `I already carry out the functions of a family physician' (p = 0.001); (ii) `They [specialist family physicians] will not be as qualified as specialists in other categories' (p = 0.005); (iii) `It will have a negative impact on general practice' (p 0.001); (iv) `It will increase competitiveness' (p

Sanguinarine.

Sanguinarine is an alkaloid found in many medicinal plants. It has diverse biological activities, including modulation of nuclear factor-kappaB and of several enzymes. It is also known to induce apoptosis, perturb microtubules, and to have antimicrobial effects. This article reviews its cardiovascular properties, including hypotensive, antiplatelet, and positive inotropic effects. Its pharmacokinetics, and toxicology, including its carcinogenic potential, are also discussed. Further pharmacological and toxicological studies with sanguinarine are needed before its therapeutic use can be considered.

Sanguinarine downregulates AT1a gene expression in a hypertensive rat model.

We studied the in vivo effects of sanguinarine in a hypertensive rat model and its effects on AT1a mRNA expression in kidney tissues. Rats received daily for 14 d sanguinarine 0.1 mg/kg (SangL) and 0.3 mg/kg (SangH), losartan 1 mg/kg by weight (Los), or DMSO (Con). Blood pressures were monitored regularly and urine volume and sodium concentration was measured on days 0, 7, and 14. On day 15, animals were anesthetized (sodium thiopentane, 50 mg/kg), blood samples for aldosterone levels were taken, and kidneys were removed for AT1a mRNA expression. Los and SangH groups showed reduced AT1a mRNA expressions by 4.22- and 5.9-fold, respectively. In the SangL group it was reduced by 2.7-fold. Decreases in systolic blood pressures mirrored decreases in AT1a mRNA expressions in all groups. Los and SangH groups showed reductions in systolic blood pressure of 12.3% and 19.3%, respectively, whereas in the SangL group, it was reduced by 8.07%. Urine output in the Los group increased (228% mean increase from days 0-14), whereas sodium excretion decreased by 69.6% (mean decrease from days 0-14). In the SangL and SangH groups, urine volumes increased significantly by 108.3% and 115% (mean increase from days 0-14), respectively. Urinary sodium excretion increased significantly by 60.9% in the SangH group. We concluded that sanguinarine reduces blood pressure in the Dahl rat because of decreased AT1 receptor expression and reduced aldosterone levels. The action of losartan on increased urinary volume and decreased sodium excretion may be attributed to reduced vasopressin secretion.

Urinary heparan sulfate proteoglycan excretion in black African women with pre-eclampsia.

BACKGROUND: The heparan sulfate proteoglycan of the glomerular basement membrane is considered to be mainly responsible for the charge selectivity of the glomerular basement membrane. Decreased heparan sulfate proteoglycan results in a decreased anionic charge of the glomerular basement membrane with increased heparan sulfate proteoglycan in the urine, and is believed to be responsible for the proteinuria in pre-eclampsia. AIM: To determine the urinary heparan and chondroitin sulfate proteoglycan levels in women with pre-eclampsia. MATERIALS AND METHODS: Eighty-four patients were studied: 28 were normotensive pregnant, 28 were nonproteinuric hypertensive, and 28 were pre-eclamptic. Urine samples were obtained and urinary glycosaminoglycan concentrations were determined using the dimethyl-methylene blue assay. Plotting absorbance against the concentrations of heparan and chondroitin sulfate proteoglycans drew a standard curve. The concentration of heparan and chondroitin sulfate proteoglycans was read-off from the linear portion of the standard curve. The standard solutions contained 25, 50, 100 and 200 mg/l heparan or chondroitin sulfate. The Mann-Whitney U-test was used to detect differences between the three groups, and the Pearson's correlation coefficient was calculated for clinical data correlation of the pre-eclamptic group. RESULTS: Urinary excretion of heparan sulfate proteoglycan (123.1 +/- 22.1 mg/l) was significantly increased in the pre-eclamptic group compared with the normotensive pregnant group (60.5 +/- 5.1 mg/l; p < 0.0001) and the hypertensive nonproteinuric group (63. 2 +/- 3.7 mg/l; p < 0.0001). Urinary chondroitin sulfate proteoglycan excretion followed a similar pattern, being significantly increased in the pre-eclamptic group (88.86 +/- 9.79 mg/l) compared with the normotensive pregnant group (49.1 +/- 8.49 mg/l; p < 0.0001) and the hypertensive nonproteinuric group (43. 9 +/- 5.7 mg/l; p < 0.0001). A significant Pearson's correlation between 24-h urine output vs. 24-h protein excretion (r = 0.51; p < 0.001), and between loss of HSPG versus 24-h urinary protein excretion (r = 0.72; p < 0.0001) was obtained in the pre-eclamptic group. CONCLUSION: This study demonstrates a reduction of glomerular charge in pre-eclampsia. The strong correlation between the severity of proteinuria and the loss of charge supports the hypothesis that the loss of glomerular charge induces structural changes of the filtration barrier, and may be the mechanism responsible for the proteinuria in pre-eclampsia. Furthermore, the elevated levels of urinary proteoglycan (heparan and chondroitin sulfate proteoglycans) in this disorder show a loss into the urine rather than a neutralization of these macromolecules.