Hypertension in pregnancy: natural history and treatment options.

Hypertensive disorders of pregnancy affect approximately 5-10% of all maternities and are major contributors of maternal and neonatal morbidity and mortality worldwide. This group of disorders encompasses chronic hypertension, as well as conditions that arise de novo in pregnancy: gestational hypertension and pre-eclampsia. The latter group is thought to be part of the same continuum but with arbitrary division. Research into the aetiology of hypertension in pregnancy have largely been focused on pre-eclampsia, with a majority of studies exploring either pregnancy-associated factors such as placental-derived or immunologic responses to pregnancy tissue, or maternal constitutional factors such as cardiovascular health and endothelial dysfunction. The evidence base for the pathophysiology and progression of hypertensive disorders in pregnancy, particularly pre-eclampsia, is reviewed. Clinical algorithms and pharmacological agents for the management of hypertension in pregnancy are summarised, with a brief focus on post-partum considerations and long-term health implications. Novel therapeutic options for the management of pre-eclampsia are also explored.

Evaluation of carbon-based nanosorbents synthesised by ethylene decomposition on stainless steel substrates as potential sequestrating materials for nickel ions in aqueous solution.

The present work covers the preparation of carbon-based nanosorbents by ethylene decomposition on stainless steel mesh without the use of external catalyst for the treatment of water containing nickel ions (Ni2+). The reaction temperature was varied from 650 to 850 degrees C, while reaction time and ethylene to nitrogen flow ratio were maintained at 30 min and 1:1 cm3/min, respectively. Results show that nanosorbents synthesised at a reaction temperature of 650 degrees C had the smallest average diameter (75 nm), largest BET surface area (68.95 m2/g) and least amount of impurity (0.98 wt.% Fe). A series of batch-sorption tests were performed to evaluate the effects of initial pH, initial metal concentration and contact time on Ni2+ removal by the nanosorbents. The equilibrium data fitted well to Freundlich isotherm. The kinetic data were best correlated to a pseudo second-order model indicating that the process was of chemisorption type. Further analysis by the Boyd kinetic model revealed that boundary layer diffusion was the controlling step. This primary study suggests that the prepared material with Freundlich constants compared well with those in the literature, is a promising sorbent for the sequestration of Ni2+ in aqueous solutions.

Relationship between vitamin D status, body composition and physical exercise of adolescent girls in Beijing.

UNLABELLED: Little is known about the prevalence of actual vitamin D deficiency in healthy school-aged adolescents, particularly in China. The aim of this study was to examine the prevalence of hypovitaminosis D and to identify whether there was any association between vitamin D status, body composition and physical exercise in 323 Chinese adolescent girls in Beijing, China (40 degrees N). INTRODUCTION: It is well recognized that persistent severe vitamin D deficiency is associated with the bone abnormalities of rickets and osteomalacia. However, there is now evidence suggesting that low vitamin D status, not previously considered to be a state of deficiency is associated with secondary hyperparathyroidism, increased bone remodelling and other clinical signs thought only to be found in severe vitamin D deficiency. Hypovitaminosis D in healthy children and adolescents has been reported frequently in many countries, especially in winter. METHODS: We performed a cross-sectional analysis of 323 Chinese adolescent girls in Beijing in winter. Mean age of the subjects was 15.0 (+/-0.4) years. About 32.8%, 68.4% and 89.2% of the subjects were at risk of vitamin D deficiency when defined as plasma concentrations of 25OHD of 25, 37.5 or 50 nmol/L, respectively. RESULTS: This cross-sectional analysis of 323 Chinese adolescent girls in Beijing in winter showed that hypovitaminosis D was common in these subjects. In addition, body mass index, milk intake, participation in organized sports and total physical activity were all significant independent determinants of vitamin D status. An inverse association was found between plasma 25OHD and intact-parathyroid hormone (iPTH) concentration. Body mass index (BMI), milk intake, participation in organized sports and total physical activity all emerged as major independent determinants of vitamin D status as assessed by plasma 25OHD concentration. Vitamin D status was positively associated with lean body mass (LBM), but there was no association with the degree of body adiposity. Regardless of the concentration of 25OHD in blood used to define vitamin D deficiency, hypovitaminosis D was common in these subjects. CONCLUSION: It is recommended that policies be developed to prevent vitamin D deficiency in adolescent girls. Further studies are needed to identify the mechanisms whereby vitamin D status is related to exercise and to body composition during growth.

Radioprotective properties of polyphenols from Phyllanthus amarus Linn.

Radioprotective activity of pure compounds isolated from the plant Phyllanthus amarus was studied using rat liver mitochondria and pBR322 plasmid DNA as an in vitro model system. These compounds were ellagitannins namely amariin, 1-galloyl-2,3-dehydrohexahydroxydiphenyl (DHHDP)-glucose, repandusinic acid, geraniin, corilagin, phyllanthusiin D, and flavonoids namely rutin, and quercetin 3-O-glucoside. The activity was then correlated with their hydroxyl and superoxide radical scavenging activity. Both ellagitannins and flavonoids effectively prevented lipid peroxidation and protein oxidation in mitochondria. The compounds also prevented radiation induced single strand breaks in pBR322 plasmid DNA. The radioprotective activity of ellagitannins and flavonoids could be due to their ability to scavenge different radicals more or less efficiently, relieving the oxidative stress. Protection conferred by flavonoids, rutin and quercetin 3-O-glucoside to rat liver mitochondria and plasmid pBR322 DNA from radiation induced damage was due to their strong hydroxyl radical scavenging activity. The inhibitory effect of ellagitannins on lipid peroxidation in liver mitochondria was due to their efficient superoxide radical scavenging ability. This is the first report about the radioprotective activity of pure ellagitannins from Phyllanthus amarus.

Biotransformation of Flavonoid Conjugates with Fatty Acids and Evaluations of Their Functionalities.

Enzymatic conjugation with fatty acids including omega-3 polyunsaturated fatty acids (ω-3 PUFAs) derived from fish oil to three citrus fruit-derived flavonoids: grapefruit extract, naringin, and neohesperidin dihydrochalcone were investigated. The conversions were achieved over 85% under the catalysis of lipase Novozyme 435 in acetone at 45°C at semi-preparative scale. The conjugates were purified via solvent partition and silica gel chromatography and achieved 90-98% in purity. The NMR analysis of the conjugates confirmed that the fatty acid carbon chain was linked onto the primary -OH group on the glucose moiety of the flavonoids. The purified flavonoid conjugates alongside their original flavonoids were analyzed for antioxidant activities via 2,2-diphenyl-1-picrylhydrazyl scavenging assay, and anti-peroxidation test via peroxide values measured during a 1-week fish oil storage trial. Vascular endothelial growth factor (VEGF) assay was conducted with 1, 10, and 100 µM of naringin and grapefruits and their conjugates, respectively, and total VEGF levels were measured at 24 and 48 h, respectively, using ELISA and dot blot analysis. The results from these functionality experiments demonstrated that flavonoid FA conjugates have at least comparable (if not higher) antioxidant activity, anti-peroxidation activity, and anti-angiogenic activity.

Pulse radiolysis, electron paramagnetic resonance spectroscopy and theoretical calculations of caffeic acid oligomer radicals.

Seven representative compounds isolated from Salvia officinalis, among them caffeic acid, the dimer rosmarinic acid and oligomers of caffeic acid, were investigated with regard to their antioxidant potential both expressed by the radical scavenging activity and the stability and structure of the intermediate radicals. Pulse-radiolytic investigation revealed very high rate constants with both hydroxyl and azide radicals. Evidence from kinetic modelling calculations suggested unusual complex behavior due to the presence of both O(4)- and O(3)-semiquinones and - in two cases - formation and decay of a hydroxyl radical adduct at the vinyl side chain. EPR spectroscopy studies, which included dihydrocaffeic acid as a model for the saturated side chains of the oligomers, confirmed that the radical structures after oxidation in slightly alkaline solutions are representing dissociated O(4)-semiquinones. While according to calculations based on hybrid density-functional theory the other radical structures are valid intermediates, they cannot be observed except by pulse radiolysis due to their fast decay.

Fluorosis prevalence among schoolchildren in a fluoridated community in Malaysia.

OBJECTIVES: This study aims to assess the magnitude of the problem of fluorosis among 10-11 year old schoolchildren in a fluoridated area in Malaysia. METHODS: An analytical cross-sectional design was adopted. Sampling of subjects was by a 2-stage systematic random sampling technique in Selangor, a fully fluoridated area. 1,343 10-11 year olds were assessed for fluorosis using the Dean's index. RESULTS: The prevalence of fluorosis was 58.7% (788 subjects); 478 (35.6%) subjects exhibited very mild fluorosis, 196 (14.6%) mild, 102 (7.6%) moderate, 12 (0.9%) severe and 555 (41.3%) no fluorosis. Tooth prevalence was 30.1%. Overall, the Community Fluorosis Index (CFI) was 0.96 and ranged from 0.23 to 1.72. Fifteen out of 30 schools had CFI > 1.0 (medium public health significance). CONCLUSIONS: The prevalence of dental fluorosis in Malaysia (mostly very mild to mild) at 58.7% is indicative of slightly above optimal levels of exposure. There were pockets of areas where fluorosis were of medium public health significance (CFI > 1.0). It must be cautioned that, fluorosis if not monitored closely, can become an increasing public health concern.

Chemical studies of proanthocyanidins and hydrolyzable tannins.

We investigated a number of natural polyphenols representing flavan-3-ols, gallotannins, and ellagitannins with regard to their antioxidant potential. For this purpose we used pulse radiolysis to determine scavenging rate constants with hydroxyl radicals and decay rates of the respective aroxyl radicals and EPR spectroscopy to identify the radicals after in situ oxidation. Using NMR spectroscopy, we could confirm phenolic coupling reactions of epigallocatechin gallate and pentagalloyl glucose after radical-induced oxidation.

Platelets of habitual smokers have reduced susceptibility to aggregating agent.

Platelet aggregation to collagen, and productions of 6-keto-prostaglandin-F1-alpha and thromboxane B2 during aggregation were measured after an overnight fast, involving both food and cigarettes, in 19 clinically healthy habitual smokers (10 or more cigarettes/day) and 23 non-smokers receiving the same diet. The subjects (all males; ages = 21-30 years) were residents of a school hostel. Mean platelet aggregation was significantly lower in smokers than non-smokers (23.2 ohms vs 31.5 ohms, p less than 0.005). Non-smokers had significantly higher mean concentration of 6-keto-prostaglandin-F1-alpha than smokers (109.8 pmol/l vs 92.3 pmol/l, p less than 0.05). The level of thromboxane B2 did not differ significantly between the two groups. These observations suggest that the role of smoking as a risk factor for ischaemic heart disease is unlikely to be related to a direct enhancement of aggregation. On the contrary, the observations seem to suggest that habitual smoking may directly reduce platelet aggregability.

Does the use of mean or median Z-score of the thyroid volume indices provide a more precise description of the iodine deficiency disorder status of a population?

Endemic iodine deficiency is largely an environmental problem affecting whole populations. Currently, thyroid volume data from a population are analyzed with the sole objective of obtaining an estimate of goitre prevalence using +97th percentile or +2 standard deviations of an appropriate reference as cut-off. This paper proposes an alternative approach to the analysis and presentation of thyroid volume data using Z-scores (standard deviation scores) of the thyroid volume indices such as thyroid volume-for-age or thyroid volume-for-body surface area. The calculation of the summary statistics of the Z-scores, such as mean or median, provides an alternative to the prevalence-based approach for expressing severity of iodine deficiency disorders (IDD). An advantage of the mean or median Z-score is that it describes the thyroid volume profile (and therefore the IDD status) of the entire population directly, unlike goitre prevalence which gives information only about the extremes of distribution. The frequency curve or histogram of the Z-scores provides a complete picture of the whole distribution. Although qualitatively similar conclusions on IDD severity can be drawn from both analytical approaches, only the Z-score system is able to capture adequately the trends or changes in thyroid size over time, and to establish whether a previously iodine-deficient community's thyroid volume profile has returned to 'normal' (as indicated by a distribution that is not significantly different from that of the reference) following intervention. As a continuous variable, Z-scores are particularly useful for the analysis of data from populations where the sample size is relatively small, or where many individuals lie outside the extreme percentiles of the reference population. In view of its advantages in the context of activities based on single and multiple measurements, the Z-score system is to be preferred for the reporting and use of thyroid volume indices. A desirable consequence of this preference is that national goals will be oriented towards an improvement of the overall thyroid volume profile of the population, rather than just a reduction of the number of individuals at the extremes.

Local versus WHO/International Council for Control of Iodine Deficiency Disorders-recommended thyroid volume reference in the assessment of iodine deficiency disorders.

OBJECTIVE: Iodine deficiency endemia is defined by the goitre prevalence and the median urinary iodine concentration in a population. Lack of local thyroid volume reference data may bring many health workers to use the European-based WHO/International Council for Control of Iodine Deficiency Disorders (ICCIDD)-recommended reference for the assessment of goitre prevalence in children in different developing countries. The present study was conducted in non-iodine-deficient areas in Malaysia to obtain local children's normative thyroid volume reference data, and to compare their usefulness with those of the WHO/ICCIDD-recommended reference for the assessment of iodine-deficiency disorders (IDD) in Malaysia. DESIGN AND METHODS: Cross-sectional thyroid ultrasonographic data of 7410 school children (4004 boys, 3406 girls), aged 7-10 years, from non-iodine-deficient areas (urban and rural) in Peninsular Malaysia were collected. Age/sex- and body surface area/sex-specific upper limits (97th percentile) of normal thyroid volume were derived. Thyroid ultrasonographic data of similar-age children from schools located in a mildly iodine-deficient area, a severely iodine-deficient area, and a non-iodine-deficient area were also collected; spot urines were obtained from these children for iodine determination. RESULTS: The goitre prevalences obtained using the local reference were consistent with the median urinary iodine concentrations in indicating the severity of IDD in the areas studied. In contrast, the results obtained using the WHO/ICCIDD-recommended reference showed lack of congruency with the median urinary iodine concentrations, and grossly underestimated the problem. The local sex-specific reference values at different ages and body surface areas are not a constant proportion of the WHO/ICCIDD-recommended reference. A further limitation of the WHO/ICCIDD-recommended reference is the lack of normative values for children with small body surface areas (<0.8m2) commonly found in the developing countries. CONCLUSION: The observations favour the use of a local reference in the screening of children for thyroid enlargement.

Ovalocytosis protects against severe malaria parasitemia in the Malayan aborigines.

The malaria parasite rates and densities were compared in 79 ovalocytic-normocytic pairs of Malayan Aborigines matched for age, sex, proximity of residence to each other, and use of bed nets when sleeping in their jungle settlement in central Peninsular Malaysia. Malaria infection was determined from thick and thin Giemsa-stained blood films collected monthly for a period of six months. Blood films from ovalocytic individuals were found to be positive for malaria less often than in persons with normal red blood cells (P less than 0.05). Malaria infections per 100 person-months at risk were 9.7 in the ovalocytic group compared with 15.19 in the normocytic group. Among individuals parasitemic at any time, heavy infections (greater than or equal to 10,000 parasites/mm3 of blood) with Plasmodium falciparum, P. vivax, and P. malariae were encountered only in normocytic subjects, which comprised approximately 12.5% of the malaria-positive individuals in this group. In an earlier survey of 629 settlers that identified subjects for the above study, the prevalence of ovalocytosis was found to increase significantly with age. The above field observations support the view that ovalocytic individuals might have a survival advantage in the face of malaria. Consideration of the ovalocytic factor is indicated in future evaluations of malaria control measures in areas where ovalocytosis is prevalent.

PIP: The malaria parasite rates and densities were compared in 79 ovalocytic-normocytic pairs of Malayan Aborigines matched for age, sex, proximity of residence to each other, and use of bednets when sleeping in their jungle settlement in central Peninsular Malaysia. Malaria infection was detected from thick and thin Giemsa-stained blood films collected monthly for a 6-month period. Blood films from ovalocytic individuals were found to be positive for malaria less often than in those individuals with normal red blood cells (p0.05). Malaria infections/100 person-months at risk were 9.7 in the ovalocytic group as compared with 15.19 in the other group. Among those parasitemic at any time, heavy infections (or= 10,000 parasites/cu.mm of blood) with Plasmodium falciparum, P. vivax, and P. malariae were seen only in normocytic subjects, approximately 12.5% of the malaria-positive persons in this group. In an earlier survey of 629 settlers who identified subjects for the above study, the prevalence of ovalocytosis was found to increase significantly with age. The above field observations support the view that ovalocytic individuals might have a survival advantage in the face of malaria. Consideration of the ovalocytic factor is indicated in future evaluations of malaria control measures in those areas where ovalocytosis is prevalent.

Flavonoid and phenolic glycosides from Salvia officinalis.

Two novel phenolic glycosides cis-p-coumaric acid 4-O-(2'-O-beta-D-apiofuranosyl)-beta-D-glucopyranoside and trans-p-coumaric acid 4-O-(2'-O-beta-D-apiofuranosyl)-beta-D-glucopyranoside were isolated and identified from Salvia officinalis together with 4-hydroxyacetophenone 4-O-(6'-O-beta-D-apiofuranosyl)-beta-D-glucopyranoside, luteolin 7-O-beta-D-glucoside, 7- and 3'-O-beta-D-glucuronide, 6-hydroxyluteolin 7-O-beta-D-glucoside and 7-O-glucuronide, and 6,8-di-C-beta-D-glucosylapigenin (vicenin-2). The luteolin glucuronides and vicenin-2 were identified as new sage constituents.

Inhibition of eukaryote signal-regulated protein kinases by plant-derived catechin-related compounds.

The cladodes of Phyllocladus trichomanoides, the bark of Pseudotsuga menziesii and the heartwood of Acacia melanoxylon contain catechin derivatives that are potent inhibitors of rat brain protein kinase C. Most of these compounds are also inhibitors of bovine heart cyclic AMP-dependent protein kinase catalytic subunit and wheat Ca(2+)-dependent protein kinase. However, these compounds are either not inhibitors or are relatively poor inhibitors of avian myosin light chain kinase. The most potent protein kinase inhibitors are the procyanidin dimer, trimer and tetramer from the bark of Pseudotsuga menziesii. These compounds are among the most potent plant-derived protein kinase inhibitors yet found.

Polyphenolics of Salvia--a review.

Salvia is an important genus widely cultivated and used in flavouring and folk medicines. The genus has attracted great interest so much so that it has been the subject of numerous chemical studies. It is a rich source of polyphenols, with an excess of 160 polyphenols having been identified, some of which are unique to the genus. A large number of these polyphenolic compounds are apparently constructed from the caffeic acid building block via a variety of condensation reactions. The nature of these polyphenols which have been reported is compiled in this report together with some bioactivity data in an effort to show the rapid development in the phytochemistry and the therapeutic applications of the Salvia species.

Nigrumin-5-p-coumarate and nigrumin-5-ferulate, two unusual nitrile-containing metabolites from black currant (Ribes nigrum) seed.

Two novel nitrile-containing compounds, nigrumin-5-p-coumarate and nigrumin-5-ferulate, together with six known flavonoids, were isolated from the seed of black currant (Ribes nigrum). The chemical structures of nigrumin-5-p-coumarate and 5-ferulate were elucidated using NMR spectroscopy as 2-trans-p-coumaroyloxymethyl-4-beta-D-glucopyranosyloxy-2(E)-butenenitrile and 2-trans-feruloyloxymethyl-4-beta-D-glucopyranosyloxy-2(E)-butenenitrile, respectively.

Inhibition of signal-regulated protein kinases by plant-derived hydrolysable tannins.

A variety of hydrolysable tannins purified from Phyllanthus amarus are potent inhibitors of rat liver cyclic AMP-dependent protein kinase catalytic subunit (cAK) with IC50 values (concentrations for 50% inhibition) in the range 0.2-1.7 microM. The three most effective compounds of this series of hydrolysable tannins have five phenolic substituents. These three compounds are also the most effective inhibitors of wheat embryo Ca(2+)-dependent protein kinase (CDPK), rat brain Ca(2+)- and phospholipid-dependent protein kinase C (PKC) and Ca(2+)-calmodulin-dependent myosin light chain kinase (MLCK). The order of sensitivity for protein kinase inhibition by the hydrolysable tannins studied is cAK > CDPK > PKC > MLCK. Thus the IC50 values for protein kinase inhibition by the most potent compound are 0.2 microM (for cAK), 1.8 microM (for CDPK), 26 microM (for PKC) and 56 microM (for MLCK) when protein kinase affinity is measured using synthetic peptide substrates. These hydrolysable tannin inhibitors found are the most specific and potent plant-derived inhibitors of cAK yet found.

Differential inhibition of eukaryote protein kinases by condensed tannins.

Condensed tannins, isolated from a variety of plant sources, were characterized according to the constituent flavans, being based on procyanidin and/or prodelphinidin and having a cis or trans stereochemistry at positions 2 and 3. All the tannin preparations are potent inhibitors of rat liver cyclic AMP-dependent protein kinase catalytic subunit (cAK) with IC50 values (concentrations for 50% inhibition) ranging from 0.009 to 0.2 microM. The tannin preparations are very good inhibitors of rat brain Ca(2+)- and phospholipid-dependent protein kinase C (PKC) (IC50 values in the range 0.3-7 microM), wheat embryo Ca(2+)-dependent protein kinase (CDPK) (IC50 values in the range 0.8-7 microM) and of calmodulin (CaM)-dependent myosin light chain kinase (MLCK) (IC50 values in the range 7-24 microM). One of the most effective preparations, that from the leaves of Ribes nigrum, has IC50 values with respect to cAK, PKC, CDPK and MLCK of 0.009, 0.6, 2.0 and 16 microM, respectively. In general, the order with respect to sensitivity to inhibition by these condensed tannins is cAK > PKC > CDPK > MLCK. The Ribes nigrum preparation is a competitive inhibitor of cAK with respect to both ATP and synthetic peptide substrate. These condensed tannin preparations are the most potent plant-derived inhibitors of cAK yet found.

The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro.

Ethyl acetate extracts of Sephadex LH20-purified proanthocyanidins of American cranberry (Vaccinium macrocarpon Ait.) exhibited potent biological activity by inhibiting adherence of uropathogenic isolates of P-fimbriated Escherichia coli bacteria to cellular surfaces containing alpha-Gal(1-->4)beta-Gal receptor sequences similar to those on epithelial cells in the urinary tract. The chemical structures of the proanthocyanidins were determined by 13C NMR, electrospray mass spectrometry, matrix-assisted laser absorption time-of-flight mass spectrometry and by acid catalyzed degradation with phloroglucinol. The proanthocyanidin molecules consisted predominantly of epicatechin units with mainly DP of 4 and 5 containing at least one A-type linkage. The procyanidin A2 was the most common terminating unit occurring about four times as frequently as the epicatechin monomer.