Serum vitamin D levels and hypogonadism in men.

There is inconsistent evidence on a possible association of vitamin D and androgen levels in men. We therefore aim to investigate the association of 25-hydroxyvitamin D (25(OH)D) with androgen levels in a cohort of middle-aged men. This cross-sectional study included 225 men with a median (interquartile range) age of 35 (30-41) years. We measured 25(OH)D, total testosterone (TT) and SHBG concentrations. Hypogonadism was defined as TT <10.4 nmol/L. We found no significant correlation of 25(OH)D and androgen levels. Furthermore, androgen levels were not significantly different across 25(OH)D quintiles. The overall prevalence of hypogonadism was 21.5% and lowest in men within 25(OH)D quintile 4 (82-102 nmol/L). We found a significantly increased risk of hypogonadism in men within the highest 25(OH)D quintile (>102 nmol/L) compared to men in quintile 4 (reference) in crude (OR 5.10, 1.51-17.24, p = 0.009) as well as in multivariate adjusted analysis (OR 9.21, 2.27-37.35, p = 0.002). We found a trend towards increased risk of hypogonadism in men within the lowest 25(OH)D quintile (≤43.9 nmol/L). In conclusion, our data suggest that men with very high 25(OH)D levels (>102 nmol/L) might be at an increased risk of hypogonadism. Furthermore, we observed a trend towards increased risk of hypogonadism in men with very low vitamin D levels indicating a U-shaped association of vitamin D levels and hypogonadism. With respect to risk of male hypogonadism, our results suggest optimal serum 25(OH)D concentrations of 82-102 nmol/L.

Development of a semi-permanent mascara technology.

Many women would like their mascara beauty benefits to be available all day, every day. One way to address this desire is through a semi-permanent mascara technology that provides full mascara benefits of long, dark beautiful lashes for multiple days. To date, products promising multi-day benefits have acted more as either 'lash dyes', providing a lash darkening benefit but failing to provide fullness and length, or waterproof mascaras that do not maintain the initial beauty look over multiple days. Here, a formulation approach is described for a mascara product that is designed to be abrasion resistant, flexible and insoluble in soap and water so that the initial beauty look is maintained for multiple days. The new semi-permanent formula technology uses rosinate polymers that have a superior combination of flexibility, abrasion resistance and water and surfactant resistance. Based on principles used by the paint industry for creating durable films, the levels of the polymers and other non-volatile ingredients are balanced such that the product forms a continuous polymer film on the eyelash. Cryo-SEM is used to demonstrate that the new semi-permanent formula technology forms a film different from those formed by current mascara products. A stretch test and rub test are used to demonstrate that the new semi-permanent formula technology has superior flexibility and abrasion resistance to current mascara products. Finally, a multi-day consumer study with daily imaging of the eyes is used to demonstrate the superior wear performance of the new semi-permanent formula technology in actual usage.

Highly sensitive determination of the polaron-induced optical absorption of organic charge-transport materials.

We examine polaron-induced absorption in organic transport materials using a highly sensitive measurement technique. A hole only device is embedded into a low-loss TE2 waveguide structure, and the current induced change of the waveguide absorption is measured. The exemplary study of 2,2('),7,7(')-tetrakis(N,N-diphenylamine)-9,9(')-spiro-bifluorene (S-TAD) reveals a very low polaron absorption cross section of sigma(p) < or = 2.6 x 10(-18) cm(2) for 560 nm < or = lambda < or = 660 nm. The accuracy of this data is unsurpassed by other techniques used for the unambiguous study of polaronic species in organic thin films.

The use of hormone replacement therapy in patients after breast cancer.

Four prospective randomized studies and at least 15 observational studies investigating hormone replacement therapy (HRT) after breast cancer are available. Only the Hormonal replacement therapy After Breast cancer: Is iT Safe (HABITS) study shows an increased risk of relapse. This is probably associated with the relatively high number of patients with HRT treatment after estrogen receptor-positive cancers as well as to the preferred use of estrogen/progestin combined preparations. As is generally known, the progestin component especially seems to be mainly responsible for the probability of increased diagnosis frequency of breast cancer. However, the patient samples in all studies investigating HRT after breast cancer are small. Therefore, HRT should only be used if alternatives, such as specific not contraindicated phyto-preparations or serotonin reuptake inhibitors, are not working. This is primarily due to forensic reasons. According to medical criteria, the data for the alternatives seem to be even more sparse, since many important questions remain unanswered, such as side effects and risks, or also regarding interactions with adjuvant hormone therapy.

[Treatment results from inpatient psychosomatic rehabilitation of Turkish migrants: a prospective study]. / Behandlungsergebnisse stationärer psychosomatischer Rehabilitation bei türkischen Migranten: Eine prospektive Studie.

Psychosomatic rehabilitation and the concluding social-medical assessment constitute a particular challenge. The aim of this study was to examine whether inpatient psychosomatic rehabilitation in the context of an integrated treatment concept, conducted in Turkish and German, is effective in the rehabilitation of Turkish migrant laborers, and what concluding socio-medical assessment results from this treatment. 195 Turkish patients--44 male and 151 female--received inpatient psychosomatic treatment for approximately 40 days. Sociodemographic, psychiatric and social-medical data were recorded, as well as Symptom Checklist (SCL-90-R) testing upon admission and discharge. A predominant number of patients were laborers, with a low level of primary education, who were afflicted with psychosocial problems and dissatisfaction with their workplace and who first came into psychosomatic treatment many years following the onset of their illness. Many of them had a clearly defined desire to retire. At the end of their admission, a significant improvement in almost all the scales of the SCL-R-90 was ascertained on the one hand, but on the other, adequate socio-medical results were hardly observed. The symptoms' improvement would confirm that the combination of service offerings in Turkish and German proved themselves. A portion of the patients (approx. 40 %) were classified subsequent to treatment as capable of working for 6 hours or more. Nevertheless, approximately approx. 75 % still sought to retire. Timely psychosomatic treatment could counteract chronification of the illness and the establishment of a steadfast desire to enter retirement, and consequently represent an improvement in the prognosis. Likewise, consistent psychosomatic training of physicians, as well as systematic prophylactic measures with the migrant laborers, should be considered.

[Malaria in the central highlands of Madagascar: control strategies]. / Paludisme sur les hautes terres centrales de Madagascar: stratégies de lutte.

The purpose of this article is to present data on malaria in the central highland plateaux of Madagascar and strategies to improve the national malaria control program. Use of rapid diagnosis strips, early home-based fever management with pre-packaged chloroquine treatment kits and proposed new therapeutic combination based on artemisinine are discussed for management of patients with high suspicion of malaria attack. Preventive measures including alternated targeted and full-house indoor spraying for vector control, use of insecticide-impregnated bednets, implementation of intermittent preventive treatment in risk groups, optimization of the epidemic early detection and warning system using the Lot Quality Assurance Sampling method for epidemiological investigation if the alert threshold is exceeded, and provision of rapid diagnosis strips are presented.

Paludisme sur les Hautes Terres Centrales de Madagascar : strategies de lutte

Le present article presente le paludisme sur les Hautes Terres Centrales de Madagascar et les strategies pour ameliorer les composantes du programme national de lutte contre le paludisme. Pour la prise en charge du patient suspect d'acces palustre; l'utilisation des bandelettes de diagnostic rapide; la prise en charge precoce a domicile par la chloroquine pre-emballee et les reflexions sur les nouvelles combinaisons therapeutiques a base d'artemisinine sont discutees. Pour les mesures de prevention; l'alternance des pulverisations intra domiciliaires ciblees et generalisees dans la lutte antivectorielle; l' utilisation de moustiquaires impregnees d'insecticides; le passage au traitement preventif intermittent pour les groupes a risque; l'amelioration du systeme de surveillance et d'alerte epidemique par l'utilisation de la methode de Lot Quality Assurance Sampling pour l'investigation epidemiologique en cas de depassement du seuil d'alerte et la mise a disposition des bandelettes de diagnostic rapide sont etudies

Matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression is not regulated by norgestimate or norelgestromin.

Steroid hormones regulate endometrial expression of matrix metalloproteinases (MMPs) and their inhibitors. Synthetic progestins are widely used in oral contraceptives and for hormone replacement therapy. To assess whether the synthetic progestins norgestimate and its derivative norelgestromin (17-deacetylnorgestimate) modulate the expression of MMPs, Ishikawa endometrial cancer cells were separately treated with 17 beta-estradiol, 17 alpha-hydroxyprogesterone, norgestimate and norelgestromin. Culture supernatants were assayed for MMPs 2, 3 and 9, and for tissue inhibitors of MMPs (TIMP-1 and TIMP-2) by enzyme-linked immunosorbent assays (ELISAs). No marked modulation of MMP-2 and TIMP-2 expression was observed upon incubation of the cells with the synthetic progestins. By ELISA, neither MMP-3 or MMP-9 nor TIMP-1 immunoreactivity was detected. Interestingly, TIMP-2 expression was down-regulated by 17 beta-estradiol and 17 alpha-hydroxyprogesterone.

Induction of androgen receptor activity by norgestimate and norelgestromin in MDA-MB 231 breast cancer cells.

The function and clinical significance of the androgen receptor (AR) in human breast cancer are still not clear. The synthetic progestins, norgestimate and norelgestromin, were designed to minimize the adverse effects such as acne, hirsuitism and metabolic changes observed with older oral contraceptives while maintaining contraceptive effectiveness and cycle control. AR-mediated effects of these synthetic progestins were studied in an in vitro transactivation assay, employing DNA co-transfection of an AR expression vector and luciferase reporter gene construct in the MDA-MB 231 human breast cancer cell line. Testosterone acetate and 5alpha-dihydrotestosterone induced the reporter gene transcription, whereas incubation of the transfected cells with the natural progestin 17alpha-hydroxyprogesterone did not markedly induce luciferase activity. The progestins norgestimate and norelgestromin exerted a very low androgenic activity. Our data suggest that norgestimate and its metabolite norelgestromin possess weak androgen-like properties. The use of these compounds for clinical application may be of great advantage in the treatment of breast cancer as well as hyperandrogenism in women.

Synthetic estrogen-mediated activation of ERK 2 intracellular signaling molecule.

Ovarian steroids are important modulators of normal cell growth and differentiation as well as of carcinogenesis. External stimuli trigger cell surface receptors, resulting in activation of central signal transduction pathways, that are mediated by members of the mitogen-activated protein kinase (MAPK) family. These in turn, indirectly regulate cellular functions such as cell proliferation, cell cycle, and maintenance of malignant phenotype. In our in vitro study, we have investigated the effects of two synthetic estrogens on ERK 2 activation. Estrogen receptor positive cells were incubated with the synthetic estrogens, ethinylestradiol (10(-9) mol/l) and 17 beta-estradiol valerate (10(-9) mol/l), epidermal growth factor (EGF) (10 ng/ml) and the natural estrogen 17 beta-estradiol (10(-9) mol/l), for 5 min. The same experiments were repeated prior to preincubation with the antiestrogen ICI 182780. ERK 2 or the active form alone were detected by immunoblotting. A cell proliferation assay was used to study the response of cells to various treatments. Time kinetics were performed to study duration of kinase activated state. Cell incubation with EGF as well as with either natural or synthetic estrogen stimulated proliferation. ICI 182780 inhibited this effect, but only in the case of estrogen. Synthetic estrogens activated MAP kinase in a time-dependent fashion, similar to 17 beta-estradiol. The estrogen receptor antagonist ICI 182780 blocked this effect. EGF induced a more pronounced and prolonged activation, even in the presence of the antiestrogen. Ethinylestradiol as used in oral contraceptives, and 17 beta-estradiol and 17 beta-estradiol valerate as used in hormone replacement therapy, are able to activate MAP kinase. This activation was blocked by an antiestrogen.

Impact of obesity and leptin levels on the secretion of estradiol, inhibin A and inhibin B during ovarian stimulation with gonadotropins.

We examined the impact of high leptin levels on the secretion of estradiol, inhibin A and inhibin B in obese and lean women during ovarian stimulation. Patients undergoing long-term pituitary suppression, ovarian stimulation and in vitro fertilization for non-endocrine reasons were included in this case-control study. Obese women (body mass index (BMI) > 28 kg/m(2); n = 17) were individually matched with lean women (BMI 20-25 kg/m(2); n = 17) for age and baseline follicle stimulating hormone and luteinizing hormone concentrations. Blood samples were collected in a previous menstrual cycle and 1-3 days apart throughout ovarian stimulation. Serum levels of estradiol, leptin, inhibin A and inhibin B were measured. Obese and lean women had similar serum concentrations of estradiol, inhibin A and inhibin B in the follicular and luteal phases of the spontaneous menstrual cycle, and throughout ovarian stimulation. Serum levels of leptin were higher in obese than in lean women, and increased during stimulation in both groups. In the obese group, area-under-the-curve (AUC) leptin levels correlated with AUC inhibin A levels. In the lean group, there was no correlation between AUC leptin levels and AUC levels of ovarian hormones. The results suggest that high leptin concentrations in vivo are not associated with impaired secretion of estradiol and dimeric inhibins during ovarian stimulation.

South-East Asian ovalocytosis among the population of the Highlands of Madagascar: a vestigé of the island's settlement.

In the Madagascar Highlands, 0.76% of children from 168 random primary schools, and 19 of 150 families from 3 villages, had oval-shaped erythrocytes. Most harboured the deletion in the band 3 gene characteristic of South-East Asian ovalocytosis. This genetic trait supports the Indonesian origin of the Madagascar settlement.

Testosterone and 5 alpha-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines.

Androgens are of biological and clinical importance for the growth and development of breast cancer in women, and the androgen receptor (AR) has been shown to be a predictor of tumor differentiation. In the present study, we investigated the relationship between AR status and testosterone and 5 alpha-dihydrotestosterone (DHT)-dependent proliferation of the human breast carcinoma cell lines MCF-7, T47-D, MDA-MB 435S and BT-20. AR status was studied by means of immunocytochemistry and Western blot analysis. All four cell lines stained positively for AR. Western blot analysis revealed a strong expression of AR in MCF-7, in contrast to BT-20 cells. According to proliferation kinetics, we observed a significant (p < or = 0.05) dose-dependent inhibition of cell growth by testosterone and DHT treatment in all four cell lines. In the estrogen receptor (ER)-negative cell lines BT-20 and MDA-MB 435S, testosterone was a more potent inhibitor of cell proliferation than DHT (p < or = 0.05), in contrast to the ER-positive cells lines MCF-7 and T47-D, in which a stronger inhibition of proliferation was achieved by DHT. A partial transformation of testosterone to estrogen in ER-positive cells might be an explanation for this effect. Our data favor a possible role of androgens in growth regulation of breast cancer. Clinical studies are needed to analyze the importance of AR as a possible predictor in response to endocrine therapy of breast cancer.

Isolation and identification of antibacterial compounds from Vernonia colorata leaves.

Vernonia colorata (Compositae) is used throughout Africa for a variety of ailments. This prompted the screening of this plant for biological activity. Previous experiments carried out in our laboratory revealed that the leaves possessed high antibacterial activity. Through conventional chromatographic techniques and bioassay-guided fractionation, the following sesquiterpene lactones were isolated and identified by spectroscopic data; vernolide (1), 11beta, 13-dihydrovernolide (2) and vernodalin (3). Only 2 is a novel compound, although its antibacterial activity is low compared to compounds 1 and 3 which had minimum inhibitory concentrations of 0.1-0.5 mg/ml against Gram-positive bacteria.

Preclinical profiles of progestins used in formulations of oral contraceptives and hormone replacement therapy.

Progestins used in oral contraceptive formulations available in the United States include norgestimate, desogestrel, norethindrone, norethindrone acetate, and levonorgestrel. Progestins used in the United States in continuous and intermittent formulations of hormone replacement therapy are norgestimate, medroxyprogesterone acetate, and norethindrone acetate. The chemical structure of a progestin determines its relative binding affinity for the progesterone and androgen receptors, as well as the sex hormone binding globulin in human serum, and determines its clinical profile. Overall, the properties of levonorgestrel or norethindrone acetate in this regard differ from norgestimate and are more conducive to androgenic stimulation. Estrogen replacement offers cardioprotective effects in postmenopausal women. Progestins are added to hormone replacement therapy to counteract the well-known increased risk of endometrial hyperplasia associated with the use of unopposed estrogen. Animal models show that for some parameters, including improvement of lipid profiles, progestins can diminish the cardioprotective effect of estrogen. Initial animal studies of norgestimate combined with estrogen do not show an attenuation of estrogenic effects.

Synthetic estrogens-mediated activation of JNK intracellular signaling molecule.

Signal transduction pathways regulate the transmission of specific signals to the cells from the surface to the nucleus. Activation of protein kinases such as JNKs (c-jun amino-terminal kinase), a subgroup of the mitogen activated protein kinase (MAPK) family, results in regulation of important cellular functions like cell growth and differentiation. The involvement of estrogens in stimulation of growth of already transformed breast cancer cells in vivo and in vitro accompanied with activation of JNKs prompted us to investigate the role of synthetic estrogens in the regulation of JNK expression. T 47D breast cancer cells were incubated with the synthetic estrogens, ethinylestradiol (10(-9)M) and 17 beta-estradiol valerate (10(-9)M), epidermal growth factor (EGF) (10 ng/ml) and the natural estrogen, 17 beta-estradiol (10(-9)M), for 5 minutes. The same experiments were repeated after pretreatment of the cells with ICI 182780 for 24 hours. EGF as well as natural and synthetic estrogens stimulated proliferation. This effect was reversed by the estrogen receptor blocker ICI 182780, but only in the case of both natural and synthetic estrogen. Like 17 beta-estradiol, synthetic estrogens induced a rapid and transient activation of JNK kinase. ICI 182780 blocked this effect, but not that mediated by EGF. Ethinylestradiol used in oral contraceptives, and 17 beta-estradiol and 17 beta-estradiol valerate for hormone replacement therapy, are able to activate JNK. The estrogen receptor is necessary for JNK activation upon estrogen stimulation.

An investigation on the biological activity of Combretum species.

Leaf extracts of 20 Combretum species, many of which are used in southern African traditional medicine, were screened for anti-inflammatory, anthelmintic, anti-bilharzia (antischistosomal) and DNA-damaging activity. Significant activity in more than one bioassay was exhibited by Combretum apiculatum, Combretum hereroense, Combretum molle and Combretum mossambicense. Ethyl acetate extracts were generally most active, followed by acetone and then water extracts.

Malaria in the highlands of Madagascar after five years of indoor house spraying of DDT.

The central region of Madagascar is a vast area of highlands (altitude 700-2000 m). Malaria transmission has re-established itself here since the last epidemic of 1985-90 and has caused the deaths of 40,000 persons according to the Minister of Health. To combat the main malaria vector in the region, Anopheles funestus, annual programmes of indoor house spraying of DDT were carried out between December 1993 and January 1998 in most rural areas at altitude 1000-1500 m. A parasitological and serological study was then conducted in the highland schools to evaluate the impact of the programme and set up a database on the region. Using a cluster-sampling method 2 independent selections were conducted (one of 130 sites, the other of 40 sites). During the study, 13,462 schoolchildren were examined, 71% living in sprayed villages. Parasite prevalence among schoolchildren declined as altitude increases, from 11% at 700-900 m to 0.4% at > 1500 m. Below 1500 m, the impact of the spraying on the prevalence of the parasite was very clear (an average decrease of from 20% to 2.7% below 1000 m and of from 4.5% without spraying to 0.8% at 1000-1500 m). Geographical analysis of the data showed that the marginal regions remained the most affected by malaria (especially outside spraying zones), and persistence of 'pockets of transmission' at 1000-1500 m, essentially in areas where spraying has never been used. In 9 schools, anti-Plasmodium antibodies were sought by indirect immunofluorescence on thick smears of parasitized red blood cells. The seroprevalence ranged from 22% to 63%, which suggests that the parasite is still circulating in the region. Even though our data show that vector control continues to be very successful in the Madagascan highlands, rapid reinfection could occur and must be monitored following spraying. To this end, the Minister for Health, with the support of the Italian Co-operation, has placed the region under epidemiological surveillance since 1997. An alert system for the timely detection of the sources of epidemics and the targeting of the antivectoral campaign is also in operation. Our study suggests that this strategy should be reinforced by the spraying of DDT in the marginal zones in order to consolidate the results obtained at higher altitudes.

Inhibition of skin 5 alpha-reductase by oral contraceptive progestins in vitro.

Androgenic disorders of female skin such as hirsutism, acne and alopecia are etiologically caused by androgen excess. Skin 5 alpha-reductase activity is a major factor influencing the manifestation of endogenous androgen excess in women. Oral contraceptives have proven useful for the treatment of androgen disorders of the skin. The mechanisms of action by which oral contraceptives correct skin androgen levels may include inhibition of 5 alpha-reductase and androgen receptor activity. We investigated the inhibitory effect of oral contraceptive progestins and ethinyl estradiol on skin 5 alpha-reductase and their influence on androgen receptor activity and affinity, using three different in vitro assay systems. It was shown that norgestimate blocked 5 alpha-reductase activity with an IC50 value of 10 microM, followed by levonorgestrel (IC50 52 microM), dienogest (IC50 55 microM), cyproterone acetate (IC50 87 microM) and gestodene (IC50 98 microM). To determine the full androgenic potential of the progestins, androgen receptor binding affinities and activation potentials were determined. The progestins norgestimate and dienogest in particular combined 5 alpha-reductase inhibition with minimal androgenic potential. These data demonstrate that the progestins norgestimate and dienogest might help in the treatment of clinical hyperandrogeny in women.