Social class-specific secular trends in height among 19-year old Polish men: 6th national surveys from 1965 till 2010.

The results presented in this study concern the assessment of the secular trend of body height in 10 % a random national sample (N = 134,224) representing all regions of Poland in 8 homogeneous social groups over 45 years in Poland (1965-2010). Very significant political, social and economic changes in Poland occurred in the period studied. The political revolution that began in Poland at the turn of the 1980s and 1990s dramatically changed the picture of social inequalities in the country. It rapidly transformed (in different directions and to a different degree) the economic situation, working conditions, lifestyles and the prestige of particular social classes and professional groups. A positive secular trend was observed in 19-year-old participants in the period analysed in all homogeneous socio-professional groups, however, with different intensity in each group. The highest body height increases in 1965-2010 were observed in the sons of farmers with post-primary father's education (7.77 cm). The lowest were observed among the sons of professionals, only 5.45 cm. Although social distances between extreme socio-economic groups significantly decreased (from 4.89 cm in 1965 to 2.76 cm in 2010), social gradients of body height, despite the improvement in the standards of living of the entire society remained exceptionally stable and unchanged for nearly half a century.

Nitric oxide synthase and cytokines gene expression analyses in Leishmania-infected RAW 264.7 cells treated with an extract of Pelargonium sidoides (Eps 7630).

A modern aqueous-ethanolic formulation of the roots of Pelargonium sidoides (Eps 7630), elaborated from the traditional herbal medicine used in areas of southern Africa, is effectively employed for the treatment of ENT and respiratory tract infections in modern phytotherapy. Previous studies have demonstrated antibacterial and immunomodulatory activities. To gain insight into the mode of action at the molecular level, gene expression analyses for the inducible nitric oxide synthase and the cytokines interleukin (IL)-1, IL-12, IL-18, tumour necrosis factor (TNF)-alpha, interferon (IFN)-alpha, and IFN-gamma, were performed using reverse transcription-polymerase chain reaction (RT-PCR). The experiments were carried out in parallel in non-infected and in Leishmania major-infected RAW 264.7 cells and the expression profiles were compared with those mediated by IFN-gamma+LPS. Eps 7630 induced low mRNA levels in non-infected cells, and it considerably up-regulated the transcript expressions in parasitised cells. Interestingly, and in contrast to activation by IFN-gamma+LPS, Eps 7630 also stimulated infected cells to produce IFN-gamma mRNA. A similar expression profile was observed for the methanol-insoluble fraction (MIF) of Eps 7630 and gallic acid, a trace constituent of the extract, while the methanol-soluble fraction and umckalin, an exclusive and representative member of the occurring coumarins, proved to be devoid of any remarkable gene-inducing capabilities. The present results provide not only convincing support for the improvement of immune functions as previously demonstrated in functional bioassays, but also evidence for activation at the transcriptional level and suggest that the underlying inducing principle is located in the MIF.

Main constituents of a commercial Drosera fluid extract and their antagonist activity at muscarinic M3 receptors in guinea-pig ileum.

The range of known constituents of Drosera species is extended by identification of myricetin 3-O-galactoside, from D. madagascariensis, and (+)-cis-isoshinanolone, obtained from a commercial fluid extract. They are accompanied by the naphthoquinones droserone and plumbagin, typical of this taxon, and a series of ubiquitous flavonols, including the rarely found gossypitrin present in the latter source. Conspicuously, the commercial form of D. peltata, non-accepted by the commission E, was found to be devoid of flavonoids. In addition, the fortuitous availability of the authentic enigmatic sample 'CON', previously isolated from D. rotundifolia, led to its characterization as common quercetin. Experiments performed on isolated guinea-pig ileum demonstrated that quercetin respectively 'CON' moderately inhibited carbachol-induced contractions at 10 microM (pD'2 5.09 +/- 0.02), while (+)-cis-isoshinanolone (100 microM) was inactive. This result indicates that quercetin derivatives may well contribute to the therapeutic use of Drosera preparations.

Antileishmanial activity of hydrolyzable tannins and their modulatory effects on nitric oxide and tumour necrosis factor-alpha release in macrophages in vitro.

A series of 27 hydrolyzable tannins and related compounds was tested for antiparasitic effects against both extracellular promastigote and intracellular amastigote Leishmania donovani organisms. In parallel, the compounds were evaluated for their immunomodulatory effects on macrophage functions, including release of nitric oxide (NO), tumour necrosis factor-alpha (TNF-alpha) and interferon (IFN)-like properties using several functional assays. Of the series of polyphenols tested, only gallic acid (54 microM NO) and its methyl ester (32 microM NO) induced murine macrophage-like RAW 264.7 cells to release NO in appreciable amounts (IFN-gamma/LPS 119 microM NO). The in vitro TNF-inducing potential of the polyphenols examined increased in the order of oligomeric ellagitannins (EC(50) > 25 microg/ml) < monomeric ellagitannins, gallotannins (EC(50) 8.5 to > 25 microg/ml) < C-glucosidic ellagitannins, dehydroellagitannins (EC(50) 0.6 - 2.8 microg/ml) at the host cell subtoxic concentration of 50 microg/ml. Furthermore, promastigotes of Leishmania donovani were assayed in the presence of these polyphenols and the results showed that none of the compounds was significantly toxic (EC(50) > 25 microg/ml) to the extracellular forms. In contrast, all polyphenols showed pronounced antileishmanial activities (EC(50) < 0.4 - 12.5 versus 7.9 microg/ml for Pentostam) against intracellular amastigotes of L. donovani residing within RAW cells. Noteworthy, most compounds exhibited low cytotoxicity against the murine host cells (EC(50) >25 microg/ml). Furthermore, some ellagitannins and the majority of dehydroellagitannins induced potent interferon-like activities as reflected by inhibition of the cytopathic effect of encephalomyocarditis virus on fibroblast L929 cells. This is the first report on hydrolyzable tannins as a new class of natural products with leishmanicidal activity including their potential for inducing the release of NO, TNF and IFN-like activity in macrophage-like RAW cells.

Proanthocyanidins and related compounds: antileishmanial activity and modulatory effects on nitric oxide and tumor necrosis factor-alpha-release in the murine macrophage-like cell line RAW 264.7.

A series of 17 proanthocyanidins and structurally related compounds was tested for activity against Leishmania donovani amastigotes and promastigotes in vitro. Most of the polyphenols significantly inhibited the intracellular survival of L. donovani amastigotes (EC50 0.8-10.6 nM) when compared with the antileishmanial drug Pentostam (EC50 10.6 nM), but all were inactive against the extracellular form (EC50 7.8 to >86 nM). Noteworthy is that all compounds exhibited only moderate or no cytotoxicity against the murine host cells (EC50 7.8 to >56 nM; >25 microg/ml). These polyphenols were further evaluated for immunomodulatory effects on macrophage functions, including release of nitric oxide (NO), tumor necrosis factor-alpha (TNF) and interferon (IFN)-like properties using several functional assays. The results showed that all compounds induced murine RAW 264.7 cells only moderately to release NO (7-26 microM) relative to the reference stimulus IFN-gamma/LPS (119 microM). The TNF-inducing potential of the polyphenols producing 50% lysis in murine L929 cells ranged from absent to 138 U/ml at the host cell subtoxic concentration of 50 microg/ml. The highest TNF-inducing activity was associated with those flavan-3-ols with galloyl groups (98-127 U/ml). For proanthocyanidins, it appeared that an increase in the flavanyl chain length did not enhance the induction of TNF-release (32-86 U/ml and below detection limits for oligomers and polymers, respectively). With interferon-like activities, phylloflavan and a prodelphinidin polymer showed appreciable cytoprotective effects, as reflected by the inhibition of the cytopathic effect of encephalomyocarditis virus on L929 fibroblast cells (38 and 36 U/ml, respectively). All remaining compounds displayed only negligible or moderate protective effects at subtoxic concentrations up to 25 microg/ml (<5 to 12 U/ml). These results indicate that proanthocyanidins and related compounds have favorable antileishmanial activity in vitro and might be considered as beneficial immunological response modifiers provided there are no bioavailability problems.

Young adult height of offspring born to rural-to-urban migrant parents and urban-born parents.

This study addresses the influence of the urban or rural origin of parents on the attained height of 19-year-old young adult males resident in urban centers. The material for the study was a 10% random sample of 19-year-old Polish conscripts born in 1976 and examined in 1995. The conscripts represented all regions of the country and all social strata. Among the total sample, only those who were born and raised in and who currently lived in cities with a population > 100,000 inhabitants were retained for analysis. They were grouped by educational level of their parents and by family size (number of children). Within limits of homogeneous groups, the heights of conscripts whose parents were both of rural origin were compared to heights of conscripts whose parents were both of urban origin. Within each of nine homogeneous groups, conscripts whose parents were both of rural origin were, on average, taller than conscripts whose parents were both of urban origin. Results were similar when the origin and educational level of either the mother or the father, in addition to family size, were considered separately.

Tannins and related compounds: killing of amastigotes of Leishmania donovani and release of nitric oxide and tumour necrosis factor alpha in macrophages in vitro.

The antileishmanial and immunomodulatory potencies of a series of 28 polyphenols were evaluated in terms of extra- and intracellular leishmanicidal activity and macrophage activation for release of nitric oxide (NO), tumour necrosis factor (TNF) and interferon (IFN)-like properties. For this, several functional bioassays were employed including an in vitro model for leishmaniasis in which murine bone marrow-derived macrophages (BMMphi) were infected with the obligate intracellular parasite Leishmania donovani, an extracellular Leishmania proliferation assay, a fibroblast-lysis assay (TNF-activity), and a biochemical assay for NO. Except for gallic acid, its methyl ester, shikimic acid and catechin (EC50 25.8-67.9 nM) all polyphenols tested significantly inhibited the intracellular survival of L. donovani amastigotes (EC50 0.4-13.9 nM) when compared with the clinically used agent, sodium stibogluconate (EC50 10.6 nM). In contrast, none of the samples proved to be directly toxic for the extracellular promastigote form of the parasite. Noteworthy, the phenolic samples showed only moderate or no cytotoxicity against the murine host cells (EC50 10 to >144 nM). Although NO is an important effector molecule in macrophage microbicidal activity, the inducing potential of the test compounds for its release was found to be very moderate ranging from 7-54 microM (IFN-gamma/LPS 119 microM). On the other hand, inhibition of NO production had no apparent effect on intracellular leishmanicidal activity of polyphenols. Their in vitro TNF-inducing potential producing 50% lysis in murine L929 cells increased in the order of simple phenols and flavanols (34-48 U/ml) < A-type proanthocyanidins (53-80 U/ml) < B-type proanthocyanidins (64-200 U/ml) < hydrolyzable tannins (287-350 U/ml) at the host cell subtoxic concentration of 50 microg/ml. Furthermore, gallic acid and some hydrolyzable tannins showed appreciable IFN-like activities (14-23 U/ml) as reflected by inhibition of the cytopathic effect of encephalomyocarditis virus on fibroblast L 929 cells. The results provide a rational basis for the recorded anti-infectious efficacy of traditionally used herbal medicines containing tannins in vivo, in the light of both only moderate direct antimicrobial activities of distinct polyphenols in vitro and the limited knowledge on their uptake in humans.

Immunomodulatory principles of Pelargonium sidoides.

Extracts and isolated constituents (coumarins and phenols) of Pelargonium sidoides DC, a plant species used in folk medicine by the Southern African native population, were evaluated for their effects on nonspecific immune functions. Although this herbal medicine is also successfully employed in modern phytotherapy in Europe to cure infectious diseases of the respiratory tract, the scientific basis of its remedial effects is still unclear. Thus, functional bioassays including an in vitro model for intracellular infection with Leishmania parasites, an extracellular Leishmania growth assay, a fibroblast-virus protection assay (IFN activity), a fibroblast-lysis assay (TNF activity) and a biochemical assay for inorganic nitric oxides (iNO) were employed. None of the test samples revealed significant activity against extracellular, promastigote Leishmania donovani, the causative agent of human visceral leishmaniasis. In contrast, apart from the coumarin samples, all the Pelargonium extracts (EC(50) <0.1-3.3 microg/mL), gallic acid (EC(50) 4.4 microg/mL) and its methyl ester (EC(50) 12.5 microg/mL) significantly reduced the intracellular survival of L. donovani amastigotes within murine macrophages. These data indicate that the samples acted indirectly on Leishmania parasites, possibly by activating leishmanicidal macrophage functions. Macrophage activation was confirmed by detection of tumour necrosis factor (TNF-alpha) and inorganic nitric oxides (iNO) in supernatants of sample-treated macrophage cultures. Synthesis of iNO is a well-known effector mechanism of macrophages against microorganisms such as Leishmania. Interestingly, blocking iNO-synthase with L-NMMA had no substantial effect on sample-induced intracellular Leishmania kill. From bioassay-guided fractionation, gallic acid and its methyl ester present in large amounts in P. sidoides and in its active extracts, were identified as the prominent immunomodulatory principle for this herbal medicine. The results, when taken together with recent reported antibacterial activity, provide a rational basis for both the traditional and the present utilization of P. sidoides in the claimed conditions.

Body size, fat distribution, menarcheal age and blood pressure in 14-year-old girls.

BACKGROUND: The relationships between body size and fatness and blood pressure are generally acknowledged. The majority of the few studies that have examined the effect of fat distribution and maturation rate on blood pressure have used secondary sex characteristics as the measure of maturity. The aim of the present study is to examine the associations between blood pressure and relative weight, fat distribution, recalled menarcheal age and occurrence of menstruation (yes/no) in a sample comprising of 1149 14-year-old girls. METHODS: Systolic and diastolic blood pressure (DBP), height, weight and body circumferences were measured using standard protocols. Fatness was expressed as body mass index (BMI, kg/m2), whereas fat distribution was estimated by using waist-to-hip ratio. The girls' maturity status was assessed from exact recalled date of menarche. One-way analysis of covariance and multiple linear regression analyses were used to determine the strength of association among systolic blood pressure (SBP), DBP and BMI, menarcheal age and indices of fat distribution. RESULTS AND CONCLUSION: Height and BMI are significantly associated with SBP. Relative weight is the most important factor related to SBP independently of chronological age and maturity status. Height and age at menarche are significantly associated with DBP. Height of 14-year-old girls shows the same strength of association with SBP and DBP, whereas maturity status negatively correlates with DBP. Fat distribution shows no effect on the level of DBP in girls.

Birth order and BMI in teenage girls.

The goal of this study was to investigate the relation of birth order to relative weight and prevalence of obesity in a group of 13-15 years old girls. In 1997, 1458 girls were examined. The height and weight measured by trained staff were recorded. Family size and birth order were obtained by a questionnaire. For the purpose of the present study, 776 and 250 girls coming from two- and three-child full families, respectively, were selected from the total sample on the basis of complete information. The Body Mass Index (kg/m2) was adjusted to reference US population (NCHS) by means of the LMS parameters. Prevalence of overweight and obesity was defined according to recommendation of the International Obesity Task Force. The effect of birth order on BMI was tested by one-way analysis of variance. Prevalence of obesity was tested by the means of Pearson chi-square. First and second born girls from two-sibling families did not show significant differences in average standardized BMI. Relative weight significantly differs among girls coming from three sibling families, decreasing along with the birth order. The first-born girls were 1.5 times at higher risk of obesity in comparison to later-born girls. Differences in the proportion of overweight girls among birth order groups showed a high significance within three sibling families.

Pelargoniins, new ellagitannins from Pelargonium reniforme.

The range of natural ellagitannins is extended by identification of five new metabolites with 1C4 glucose core, designated as pelargoniins A-D and isocorilagin, and the new phyllanthusiin E methyl ester. They are accompanied in the aerial parts of Pelargonium reniforme by two known structurally related metabolites, corilagin and phyllanthusiin C, two phenolcarboxylic acids, brevifolincarboxylic acid and phyllanthusiin E, the gallotannin 1-O-galloyl-beta-D-glucopyranose, and the ellagitannins strictinin and isostrictinin having a 4C1-glucose core. The structures of these compounds were established from spectroscopic studies. This is the first example of the co-occurrence of ellagitannins with 4C1 and 1C4 glucopyranose core demonstrated for a member of the Geraniaceae.

Antifungal effects of hydrolysable tannins and related compounds on dermatophytes, mould fungi and yeasts.

A series of hydrolysable tannins and related compounds was evaluated for antifungal activities against filamentous fungi (Epidermophyton floccosum; Microsporum canis; Microsporum gypseum; Trichophyton mentagrophytes; Trichophyton rubrum; Trichophyton tonsurans; Trichophyton terrestre; Penicillium italicum; Aspergillus fumigatus; Mucor racemosus; Rhizopus nigricans) and opportunistic yeasts (Candida albicans; Candida glabrata; Candidata krusei; Cryptococcus neoformans), using the agar dilution method. While all samples had no activity against the filamentous fungi in concentrations of 1.1-5.9 microM (1000 microg/ml), the phenolic compounds displayed significant potencies against all the opportunistic yeasts tested but C. albicans, with minimum inhibitory concentrations ranging from 0.02 to 0.1 microM (16-125 microg/ml). Although the presence of galloyl groups in flavonoids did not necessarily produce activity, this structural element, an HHDP moiety or its oxidatively modified entity proved to be an important structural feature of hydrolysable tannins. Comparison of dilution methods provided strong evidence of dependence of MIC values on the test method. Employing the microdilution broth method, the ellagitannin corilagin (MIC 0.8 nM) was found to be similarly potentially active as amphotericin B (MIC 0.5 nM) and sertaconazole (MIC 0.9 nM) against Candida glabrata strains. The order of effectiveness observed being 64- and 4-8-fold increased for corilagin and the reference compounds respectively, when compared with that of the agar dilution test.

Parental education, body mass index and prevalence of obesity among 14-year-old boys between 1987 and 1997 in Wroclaw, Poland.

The main aim of this study was to examine changes in relative weight and prevalence of obesity across a ten-year period among 14-year-old boys according to parental education level. Data from two surveys, carried out in 1987 and 1997, of boys attending the 7th grade of primary schools in Wroclaw were used in the analysis. The heights and weights of 3165 boys aged 14 years selected from cohort of 6969 7th and 8th grade boys from all primary schools of the city Wroclaw were used. The data of the second sample of 14-year-old boys (n = 1014) were obtained from a health examination study carried out in the Silesian Centre for Preventive Medicine, 'DOLMED', in Wroclaw in 1997. All boys attended the 7th grade of 34 randomly selected primary schools from a total of 129 schools in the city of Wroclaw. Social status was assessed on the basis of parental education level scored to four categories: university, secondary school, trade school, and elementary school. The prevalence of overweight and obesity was defined as the percentage of children above the 85th and 95th percentiles of the body mass index (BMI), the means of which were 21.27 and 23.75 kg/m2 respectively. Prevalence of overweight among boys is slightly lower in the 1997 sample, whereas the prevalence of obesity shows the opposite trend and is higher by more than one percent in comparison with the 1987 sample. Similar trends of declining medians and increasing variance are observed in all educational groups. The differences in medians between the two samples within educational groups did not achieve statistical significance for the groups with parents with education at elementary level and fathers with university education. There is a trend toward increasing prevalence of obesity across the decade considered, according to father's education level. With respect to mother's education levels, the most dramatic changes in BMI and obesity occurred in the elementary education group, where the percentage of obese subjects increased more than twofold. A significant increase is also observed in the group with parents attaining university education.

Antibacterial activity of simple coumarins: structural requirements for biological activity.

The antibacterial activity of a series of simple coumarins was evaluated against 8 microorganisms, including three Gram-positive (Staphylococcus aureus, beta-hemolytic Streptococcus and Streptococcus pneumoniae) and five Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Haemophilus influenzae), using the microdilution broth method. The coumarins tested showed broad diversity regarding growth inhibitory activity with minimum inhibitory concentrations ranging from 0.9 to > 12.4 microM. This study, presenting the first systematic analysis of structure-activity relationships among this group of coumarins, revealed some interesting structural requirements. While coumarins with a methoxy function at C-7 and, if present, an OH group at either the C-6 or C-8 position are invariably effective against the spectrum of tested standard bacteria (Gram-negative microorganisms including the Gram-positive bacterium Staphylococcus aureus), the presence of an aromatic dimethoxy arrangement is apparently favourable against those microorganisms which require special growth factors (beta-hemolytic Streptococcus, Streptococcus pneumoniae and Haemophilus influenzae). A combination of these structural features, two methoxy functions and at least one additional phenolic group as reflected by the highly oxygenated coumarins, identify promising candidates with antibacterial broad-spectrum activity.

In vitro leishmanicidal activity of aurones.

A series of aurones with drug-potential for Leishmania infections was identified in vitro using both a direct cytotoxicity assay against extracellular promastigotes of Leishmania donovani, L. infantum, L. enriettii, and L. major, and a test against intracellular amastigote forms of L. donovani residing within murine macrophages. The most active aurone (6-hydroxy-2-[phenylmethylene]-3(2H)-benzofuranone) had an EC50 of 0.45 microgram/ml in the extra-, and an EC50 of 1.40 micrograms/ml in the intracellular assay. Other aurones were active between 0.06-12.50 micrograms/ml and 0.04-7.81 micrograms/ml, respectively. When tested against murine bone marrow-derived macrophages as a mammalian host cell control, the compounds showed only moderate cytotoxicity (EC50 2.32 to > 25.0 micrograms/ml). This is the first report on aurones as a new class of natural products with leishmanicidal activity.

Study on the composition of the volatile fraction of Hamamelis virginiana.

The volatile fractions, obtained by water distillation from the leaves and bark of Hamamelis virginiana L. were analysed in detail by GC-MS. About 175 (leaves) and 168 (bark) compounds have been identified or at least partly characterized on the basis of a computerized database (SeKoMS). The dominating substances were represented by a homologous series of alkanes, alkenes, aliphatic alcohols, related aldehydes, ketones, and fatty acid esters. Importantly, significant differences in the terpenoid and phenylpropanoid patterns of the products obtained from the bark and leaves are apparent: whereas the product of bark distillation was found to typically contain phenylpropanoids and mainly sesquiterpenoids, that obtained from the leaves included some distinct monoterpenoids detected in comparably higher amounts. The chemical composition of the volatiles, when taken together with the absence of specific accumulation sites of lipophilics, emphasizes the definition "volatile fraction" rather than "essential oil".

Dual inhibitory activities of tannins from Hamamelis virginiana and related polyphenols on 5-lipoxygenase and lyso-PAF: acetyl-CoA acetyltransferase.

In the present study, the effects of tannins obtained from various plant sources on the activity of 5-LOX and AT were examined. With IC50 values ranging from 1.0 to 18.7 muM, hamamelitannin and the galloylated proanthocyanidins isolated from Hamamelis virginiana L. were found to be most potent inhibitors of 5-LOX. Unlike the 5-LOX study, hamamelitannin proved to be ineffective in the AT assay. Potent candidates are represented by the group of B-type proanthocyanidins. Structure-activity relationships regarding the in vitro inhibitory potency of the polyphenols in the biological assays are discussed.