[Deodorants and antiperspirants]. / Déodorants et antitranspirants.

The terms deodorants and antiperspirants very frequently used interchangeably despite the fact that they employ completely different active substances and mechanisms of action. Antiperspirants are necessarily deodorants due to the lack of substrate to decompose. They nevertheless represent a group of very specific substances that create particular problems due to the presence of aluminium chlorohydrate, or ACH, (Al2(OH)5Cl, 2H2O), aluminium sesquichlorohydrate and aluminium-zirconium complex, which, after hydrolysis, causes intense acidification of the skin, hence the importance of inclusion of emollients and pH regulators in formulations. Moreover, systemic aluminium is thought to be genotoxic and to promote breast cancer, and it is thus at the centre of numerous scientific controversies. Nevertheless, its potential toxicity following topical application is related to its ability to penetrate skin, which is as yet poorly understood but considered very low, a fact that may provide some degree of reassurance regarding its use in cosmetic products. Its role in Alzheimer's disease has not been proven. On the other hand, zirconium salts are considered toxic and are partly regulated in Europe. The problems associated with deodorants are those arising from the presence of antiseptics (triclosan, usnic acid) capable of inducing bacterial resistance, but more particularly, the presence of axillary dermatitis due to the allergenic potential of the fragrances and essential oils used (e.g. isoeugenol, citronellal, lyral, cinnamic aldehyde, etc.).

[Self-tanning and sunless tanning products]. / Autobronzants et bronzants artificiels.

Practically all currently available self-tanning products have as their active ingredient dihydroxyacetone (DHA), which may or may not be combined with erythrulose, tyrosine derivatives, and occasionally a naphthoquinone. The resulting skin tone, which resembles a natural tan, is due to chemical combination of the DHA with amino acids in the skin through the Maillard reaction. Polymer pigments known as melanoidins are formed and are fixed in the stratum corneum, where they remain until corneocyte desquamation occurs. The colouring thus achieved is semi-permanent and is well tolerated by skin. While the formulation of such products is complex and their storage difficult, no other substances provide more satisfactory or more lasting results.

In vitro antiviral activity of Brazilian plants (Maytenus ilicifolia and Aniba rosaeodora) against bovine herpesvirus type 5 and avian metapneumovirus.

CONTEXT: Medicinal plants are well known for their use in traditional folk medicine as treatments for many diseases including infectious diseases. OBJECTIVE: Six Brazilian medicinal plant species were subjected to an antiviral screening bioassay to investigate and evaluate their biological activities against five viruses: bovine herpesvirus type 5 (BHV-5), avian metapneumovirus (aMPV), murine hepatitis virus type 3, porcine parvovirus and bovine respiratory syncytial virus. MATERIALS AND METHODS: The antiviral activity was determined by a titration technique that depends on the ability of plant extract dilutions (25 or 2.5 µg/mL) to inhibit the viral induced cytopathic effect and the extracts' inhibition percentage (IP). RESULTS: Two medicinal plant species showed potential antiviral activity. The Aniba rosaeodora Ducke (Lauraceae) extract had the best results, with 90% inhibition of viral growth at 2.5 µg/mL when the extract was added during the replication period of the aMPV infection cycle. The Maytenus ilicifolia (Schrad.) Planch. (Celastraceae) extracts at a concentration of 2.5 µg/mL exhibited antiviral activity during the attachment phase of BHV-5 (IP = 100%). DISCUSSION AND CONCLUSION: The biomonitored fractionation of the active extracts from M. ilicifolia and A. rosaeodora could be a potential tool for identifying their active compounds and determining the exact mechanism of action.

Development of new positive-selection RIVET tools: detection of induced promoters by the excision-based transcriptional activation of an aacCI (GmR)-gfp fusion.

RIVET (Recombination Based in vivo Expression Technology) is a powerful genetic tool originally conceived for the identification of genes induced in complex biological niches where conventional transcriptomics is difficult to use. With a broader application, genetic recombination-based technologies have also been used, in combination with regulatory proteins and specific transcriptional regulators, for the development of highly sensitive biosensor systems. RIVET systems generally comprise two modules: a promoter-trap cassette generating genomic transcriptional fusions to the tnpR gene encoding the Tn-γδ TnpR resolvase, and a reporter cassette carrying res-flanked selection markers that are excised upon expression of tnpR to produce an irreversible, inheritable phenotypic change. We report here the construction and validation of a new set of positive-selection RIVET systems that, upon induction of the promoter-trap module, generate the transcriptional activation of an antibiotic-resistant and a green-fluorescent phenotype. Two classes of promoter-trap tools were constructed to generate transcriptional fusions to tnpR: one based on the use of a narrow-host-range plasmid (pRIVET-I), integrative in several Gram-negative bacteria, and the other based on the use of a broad-host-range plasmid (pRIVET-R). The system was evaluated in the model soil bacterium Sinorhizobium meliloti, where a clear-cut phenotypic transition from Nm(R)-Gm(S)-GFP(-) to Nm(S)-Gm(R)-GFP(+) occurred upon expression of tnpR. A S. meliloti integrative RIVET library was constructed in pRIVET-I and, as expected, changes in the extracellular conditions (e.g., salt stress) triggered a significant increase in the appearance of Gm(R)-GFP(+) (excised) clones. The sacB-independent positive-selection RIVET systems here described provide suitable basic tools both for the construction of new recombination-based biosensors and for the search of bacterial markers induced when microorganisms colonize and invade complex environments and eukaryotic hosts.

Poly-epsilon-caprolactone nanocapsules containing octyl methoxycinnamate: preparation and characterization.

This study investigates the different nanocapsules (NCs) made of poly-epsilon-caprolactone (PCL) containing the lipophilic sunscreen Escalol 557 [octyl methoxycinnamate (OMC)] and analyzes the influence of nanoparticle-based systems on light-induced decomposition of the sunscreen agent. The NCs were designed and prepared by the solvent displacement method. Formulation parameters, such as the nature and volume of the organic and aqueous phase and the nature and concentration of the surfactants and polymer, have relevant implications on NC elaboration. We investigated the influence of several technological (stirring speed: 300-800 rpm) and formulation factors [polymer amount, 195-244.5 mg; surfactant, Tween 85 (Polysorbate 85), Montanox 80 (Polysorbate 80), and Synperonic PE/F68 (Poloxamer 188) as stabilizing agents; and volume of the organic phase, 20-30 mL of acetone] on the particle size and the OMC loading capacity of the formulations--encapsulation efficiency and yield. The sizes of NC obtained were in the range of 309 to 1042 nm, the encapsulation efficiencies ranged from 93.82% to 99.97%, and yields of NC encapsulation ranged from 48.12% to 86.28%. Of all the preset experimental conditions, Montanox 80, 30 mL of acetone, 244.5 mg of polymer, and a stirring speed of 350 rpm have been selected as the best in this experimental design study. The experimental conditions selected to obtain OMC-loaded NC of 374 nm resulted in a high entrapment percentage (97.52%) and yield (82.95%). The PCL nanoparticles loaded with OMC were effective in reducing light-induced degradation of the sunscreen agent.

Influence of encapsulation on the in vitro percutaneous absorption of octyl methoxycinnamate.

The purpose of this study was to evaluate the in vitro transdermal permeation and skin accumulation of one ultraviolet (UV) absorber-octyl methoxycinnamate (OMC)-through pig skin and to determine the quantity of OMC in the skin surface and different pig skin layers (stratum corneum, viable epidermis, dermis, and receptor fluid). Four cases have been considered: the application of oil-in-water (O/W) and water-in-oil (W/O) emulsions containing the same filter free and encapsulated in nanocapsules (NC). The influence of the carrier on the percutaneous penetration was studied. Data showed that UV absorber exhibited increases in skin accumulation when is formulated in emulsions in free form. Skin accumulation of OMC-free in the emulsions was significantly (P < 0.05) greater than that of OMC-encapsulated for all formulations investigated. OMC-free skin accumulation ranged from 127.8 +/- 22.8 microg/cm(2) (O/W emulsion) to 172.1 +/- 12.9 microg/cm(2) (W/O emulsion). OMC-encapsulated skin accumulation ranged from 50.3 +/- 13.1 microg/cm(2) to 43.0 +/- 6.5 microg/cm(2) at NC-O/W and NC-W/O, respectively. No significant differences were found in the transdermal permeation of cinnamate for any of the formulations tested. The results of this study demonstrate that the inclusion of OMC-encapsulated in sunscreen formulations decreases the skin accumulation of the cinnamate since the in vitro release mechanism of OMC-nanocapsules is governed by hydrophobicity and crystallinity of the polymer and by the high lipophilicity of the drug. The crystallinity of the polymer have the ability of reflecting and scattering UV radiation on their own thus leading to photoprotection without the need for molecular sunscreens.

[Biochemical analysis of epidermal lipids]. / Analyse biochimique des lipides épidermiques.

According to the knowledge acquired some 15 years ago, the cutaneous lipids may be classified into 2 families: the "neutral" lipids, represented by cholesterol, cholesterol esters, cholesterol sulphate, triglycerides, free fatty acids, squalen and alcanes, and the "polar" lipids including phospholipids (phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, sphingomyeline) and sphingolipids (ceramides I-VII, monohexosylceramides). From the functional point of view, free fatty acids, cholesterol, and ceramides organised in layers are the most important components of intercellular spaces of the stratum corneum. Analytic methods have been recently developed to help understand the structural organisation of these various molecules within the horny layer and their influence on the epidermal barrier function. Raman microspectroscopy or X-ray diffraction are most frequently used. Differential calorimetry and fluorescence or infrared spectroscopy provide complementary information. The principal findings are: lamellar structure depends on the presence of ceramides supplemented by adequate quantities of free fatty acids and cholesterol; ceramide chains interact to provide the ordered structure and ceramide-1 is necessary for stabilisation of lipid layers; cholesterol may regulate the molecular mobility of hydrocarbon chains within the bi-layers. Knowledge of the molecular structure of the barrier lipids finds several applications, e.g.: in pharmacology--conception of new formulations adapted for percutaneous and topical application of drugs; in dermatology--comprehension of physiopathologic mechanisms of various dermatoses; in biotechnology--development of skin substitutes with valid stratum corneum barrier; in cosmetics--choice of best formulations suited for reconstruction of the intercellular lipid substance.

Flaxseed consumption influences endogenous hormone concentrations in postmenopausal women.

Lignans, similar in structure to endogenous sex steroid hormones, may act in vivo to alter hormone metabolism and subsequent cancer risk. The objective of this study was to examine effects of dietary intake of a lignan-rich plant food (flaxseed) on serum concentrations of endogenous hormones and binding proteins (estrone, estrone sulfate, 17 beta-estradiol, sex hormone-binding globulin, progesterone, prolactin, dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, testosterone, and free testosterone) in postmenopausal women. This randomized, crossover trial consisted of three seven-week feeding periods, during which 28 postmenopausal women, aged 52-82 yr, consumed their habitual diets plus 0, 5, or 10 g of ground flaxseed. Serum samples collected during the last week of each feeding period were analyzed for serum hormones using standard diagnostic kits. The flaxseed diets significantly reduced serum concentrations of 17 beta-estradiol by 3.26 pg/ml (12.06 pmol/l) and estrone sulfate by 0.09 ng/ml (0.42 nmol/l) and increased prolactin by 1.92 micrograms/l (0.05 IU/ml). Serum concentrations of androstenedione, estrone, sex hormone-binding globulin, progesterone, testosterone, free testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were not altered with flaxseed feeding. In this group of postmenopausal women, consuming flaxseed in addition to their habitual diets influenced their endogenous hormone metabolism by decreasing serum 17 beta-estradiol and estrone sulfate and increasing serum prolactin concentrations.

Plasma alpha1-antichymotrypsin in Alzheimer's disease; relationships with APOE genotypes.

Inflammatory processes are thought to be important contributors to the pathogenesis of Alzheimer's disease (AD). alpha1-antichymotrypsin (ACT) is a proteinase inhibitor characteristic of acute-phase inflammation and has been identified in amyloid plaques. We analyzed the plasma ACT levels in a sample of subjects with late-onset AD and correspondent controls. Plasma ACT was higher in AD patients (62.8 +/- 20.2 mg/dl) than in controls (58.8 +/- 18.1 mg/dl), but not significantly (P = 0.13). In the AD patients regression analysis showed a positive linear relationship between ACT levels and duration of the disease (P = 0.037). Increased ACT concentrations (64.6 +/- 21.2 mg/dl) were also found in patients with greater cognitive impairment (MMSE scores < 20), but since this factor depends on the duration of the disease as well, our present data seem to indicate a complex relationship involving elevated ACT levels, disease duration and cognitive impairment. Plasma ACT was found to differ significantly according to APOE genotypes (P = 0.017), the highest levels being associated to E3-E3 homozygotes (66.1 +/- 17.8 mg/dl) and the lowest to E4-E3 subjects (53.1 +/- 18.2 mg/dl). In patients not carrying APOE*4 allele the ACT levels were higher than in controls (P = 0.014), and the relationship between ACT and disease duration was stronger than that observed in the total AD sample (P = 0.003), but it was absent in those carrying APOE*4 (P = 0.67). Taken together our results seem to suggest that inflammation is a relevant factor in AD pathogenesis for subjects with E3-E3 and E3-E2 genotypes but less important for APOE*4 carrying subjects.

Polymorphisms of the apolipoprotein E gene regulatory region and of the LDL receptor gene in late-onset Alzheimer's disease in relation to the plasma lipidic pattern.

Two new polymorphisms in the regulatory region of the apolipoprotein E gene, -491 A/T and -427 T/C, have been reported to be associated with the risk of Alzheimer's disease (AD). Moreover, in vitro studies suggest that the two polymorphisms modulate the levels of apoE protein expression. We examined these two polymorphisms, as well as the MspI polymorphism in the LDL receptor gene, in a series of elderly patients with late-onset sporadic AD and in an age-matched control group but failed to find any kind of association between these genetic features and an increased risk of AD. In the same samples we investigated the relationships between various genotypes and plasma lipid levels. Since the well-known effect of the three-allelic APOE polymorphism on plasma lipid levels could mask the effect of other polymorphisms, the analyses were performed taking into account the APOE genotype. The two regulatory region polymorphisms had significant effects only on the apoE levels. The -427 TT homozygotes had lower, and the -491 AA homozygotes had higher levels of apoE than other genotypes. This result confirmed in vivo the already observed in vitro effects of -491 A/T and -427 T/C polymorphisms on APOE promoter transcription activity.

Flaxseed influences urinary lignan excretion in a dose-dependent manner in postmenopausal women.

Dietary estrogens, such as lignans, are similar in structure to endogenous sex steroid hormones and may act in vivo to alter hormone metabolism and subsequent cancer risk. The objective of this study was to examine the effect of dietary intake of a lignan-rich plant food (flaxseed) on urinary lignan excretion in postmenopausal women. This randomized, cross-over trial consisted of three 7-week feeding periods during which 31 healthy postmenopausal women, ages 52-82 years, consumed their habitual diets plus 0, 5, or 10 grams of ground flaxseed per day. Urine samples collected for 2 consecutive days during the last week of each feeding period were analyzed for lignan content (enterodiol, enterolactone, and matairesinol) by isotope dilution gas chromatography/mass spectrometry. Compared with the 0-gram flaxseed diet, consumption of 5 or 10 grams of flaxseed significantly increased excretion of enterodiol by 1,009 and 2,867 nmol/day, respectively; significantly increased excretion of enterolactone by 21,242 and 52,826 nmol/day, respectively; and significantly increased excretion of total lignans (enterodiol + enterolactone + matairesinol) by 24,333 and 60,640 nmol/day, respectively. Excretion of matairesinol was not significantly altered by flaxseed consumption. Consumption of flax, a significant source of dietary estrogens, in addition to their habitual diets increased excretion of enterodiol and enterolactone, but not matairesinol, in a dose-dependent manner in this group of postmenopausal women. Urinary excretion of lignan metabolites is a dose-dependent biomarker of flaxseed intake within the context of a habitual diet.

The effect of flaxseed and wheat bran consumption on urinary estrogen metabolites in premenopausal women.

Estrogen is metabolized along two competing pathways to form the 2-hydroxylated and the 16alpha-hydroxylated metabolites. Based on proposed differences in biological activities, the ratio of these metabolites, 2-hydroxyestrogen:16alpha-hydroxyestrone (2:16alpha-OHE1), has been used as a biomarker for breast cancer risk. Women with an elevated 2:16alpha-OHE1 ratio are hypothesized to be at a decreased risk of breast cancer. Flaxseed, the most significant source of plant lignans, and wheat bran, an excellent source of dietary fiber, have both been shown to have chemoprotective benefits. Some of these benefits may be attributable to their influence on endogenous sex hormone production and metabolism. We examined the effect of flaxseed consumption alone and in combination with wheat bran on urinary estrogen metabolites in premenopausal women. Sixteen premenopausal women were studied for four feeding treatments lasting two menstrual cycles each in a randomized cross-over design. During the four feeding treatments, subjects consumed their usual diets supplemented with baked goods containing no flaxseed or wheat bran, 10 g of flaxseed, 28 g of wheat bran, or 10 g of flaxseed plus 28 g of wheat bran/day. Urinary excretion of 2-hydroxyestrogen and 16alpha-hydroxyestrone, as well as their ratio, 2:16alpha-OHE1, were measured by enzyme immunoassay. Flaxseed supplementation significantly increased the urinary 2:16alpha-OHE1 ratio (P = 0.034), but wheat bran had no effect. These results suggest that flaxseed may be chemoprotective in premenopausal women.

Effects of soy intake on sex hormone metabolism in premenopausal women.

Studies suggest that phytoestrogens in soy products may impart hormonal effects that protect women against breast cancer. Limited research suggests that intake of soy products high in isoflavonoid phytoestrogens affects sex hormone metabolism, but it is unknown whether phytoestrogens in soy have any effect on menstrual function or serum sex hormones in women on common hormone therapies, such as oral contraceptives (OC). We studied the effects of soy in 36 premenopausal women, 20 of whom used OC. Subjects consumed their normal diet for two menstrual cycles and added a soy beverage containing 20 g of protein and 38 mg of total isoflavones to their usual diet for another two menstrual cycles. No significant differences were observed in serum estrone, estradiol, sex hormone-binding globulin, dehydroepiandrosterone sulfate, prolactin, or progesterone concentrations with soy feeding in the non-OC or the OC group. No changes in menstrual cycle length or the urinary estrogen metabolite ratio of 2-hydroxyestrone to 16 alpha-hydroxyestrone were seen with soy feeding in the non-OC or the OC group. Levels of urinary estrogen metabolites were significantly different between the non-OC and the OC group. Thus soy consumption had no significant effect on the menstrual cycle, serum sex hormones, or urinary estrogen metabolite ratio in premenopausal OC or non-OC users.

Plausible mechanisms for the protectiveness of whole grains.

Dietary guidelines recommend the consumption of whole grains to prevent chronic diseases. Epidemiologic studies support the theory that whole grains are protective against cancer, especially gastrointestinal cancers such as gastric and colon can-cer, and cardiovascular disease. Components in whole grains that may be protective include compounds that affect the gut environment, such as dietary fiber, resistant starch, and oligosaccharides. Whole grains are also rich in compounds that function as antioxidants, such as trace minerals and phenolic compounds, and phytoestrogens, with potential hormonal effects. Other potential mechanisms whereby whole grains may protect against disease include binding of carcinogens and modulation of the glycemic response. Clearly, the range of protective substances in whole grains is impressive and advice to consume additional whole grains is justified. Further study is needed regarding the mechanisms behind this protection so that the most potent protective components of whole grains will be maintained when developing whole grains into acceptable food products for the public.

Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women.

Flaxseed, the richest known source of plant lignans, has been shown to have chemoprotective effects in animal and cell studies. Some of its effects may be mediated through its influence on endogenous hormone production and metabolism. Two competing pathways in estrogen metabolism involve production of the 2-hydroxylated and 16 alpha-hydroxylated metabolites. Because of the proposed differences in biological activities of these metabolites, the balance of the two pathways has been used as a biomarker for breast cancer risk. We examined the effects of flaxseed consumption on urinary estrogen metabolite excretion in postmenopausal women. Twenty-eight postmenopausal women were studied for three seven-week feeding periods in a randomized crossover design. During the feeding periods, subjects consumed their usual diets plus ground flaxseed (0, 5, or 10 g/day). Urinary excretion of the estrogen metabolites 2-hydroxyestrogen (2-OHEstrogen) and 16 alpha-hydroxyestrone (16 alpha-OHE1) as well as their ratio, 2/16 alpha-OHE1, was measured by enzyme immunoassay. Flaxseed supplementation significantly increased urinary 2-OHEstrogen excretion (p < 0.0005) and the urinary 2/16 alpha-OHE1 ratio (p < 0.05) in a linear, dose-response fashion. There were no significant differences in urinary 16 alpha-OHE1 excretion. These results suggest that flaxseed may have chemoprotective effects in postmenopausal women.

Plasma levels of apolipoprotein E and genetic markers in elderly patients with Alzheimer's disease.

Besides apolipoprotein E (APOE) polymorphism, whose association with Alzheimer's disease (AD) has been confirmed in most of the numerous population samples studied, other markers have been investigated. In most cases the association firstly described was not confirmed in subsequent works. Since it is important to examine these associations in as many populations as possible, we investigated APOE, APOC1, APOC2, alpha-1 antichymotrypsin (ACT) and presenilin-1 (PS-1) polymorphisms in a series of elderly patients with late-onset sporadic AD from Northern Italy and in a sex and age-matched control group. We could not confirm the significantly higher frequency of the ACT*A allele among carriers of APOE e*4 allele described elsewhere, although a similar trend was observed. The APOC2 and the PS-1 distributions were similar between patients and controls. However, we observed a significant difference in the genotype and allele frequencies of APOE and APOC1: patients had higher e*4 and C1*2 allele frequencies. This finding confirms the important role for APOE in AD occurrence. In addition, APOC1 seems to be an interesting marker because, though in strict linkage disequilibrium with APOE, it seems to play an independent role in AD risk. In contrast to previously reported data, plasma apoE concentrations were similar in patients and in controls. An interaction between APOE and APOC1 polymorphisms and apoE levels was observed in patients: subjects carrying the APOE E3/E2 or the APOC1 2-2 genotype have higher apoE concentrations than those who do not.

Urinary isoflavonoid and lignan excretion on a Western diet: relation to soy, vegetable, and fruit intake.

Dietary isoflavone and lignan phytoestrogens are potential chemopreventive agents. This has led to a need to monitor exposure to these compounds in human populations and to determine which components of a mixed diet contribute to the exposure. Typically, urinary isoflavonoid excretion is associated with soy consumption and that of lignans is associated with whole grains. However, other plant foods are known to contain phytoestrogen precursors. The purpose of this study was to examine the association between urinary isoflavonoid and lignan excretion and intakes of vegetables and fruits (V&F). Isoflavonoids (genistein, daidzein, O-desmethylangolensin, and equol) and lignans (enterolactone, enterodiol, and matairesinol) were measured in urine collected for 3 days from 49 male and 49 female volunteers (age, 18-37 years) reporting a wide range of habitual V&F intakes. Dietary intakes were assessed using 5-day diet records and a food frequency questionnaire. V&F groupings (total V&F, total V, total F, soyfoods, and V&F grouped by botanical families) were used to assess the relationship between V&F intake and urinary isoflavonoid and lignan excretion. Pearson correlations were performed. Intake of soyfoods was correlated significantly with urinary genistein (r = 0.40; P = 0.0001), O-desmethylangolensin (r = 0.37; P = 0.0002), daidzein (r = 034; P = 0.0007), and the sum of isoflavonoids (r = 0.39; P = 0.0001). There was no association between equol excretion and soy intake or between the isoflavonoids and any other V&F groupings. In addition, isoflavonoid excretion was correlated positively with intake of high-fat and processed meats, particularly among men who did not consume soy. This suggests that, even in the United States, on a Western diet, soyfoods are the primary contributors to isoflavone intake; however, additional "hidden sources" of soy may also contribute to exposure. In contrast, a variety of fiber-containing foods contributed to lignan excretion; the sum of the urinary lignans, enterodiol, enterolactone, and matairesinol, was associated with intake of total F (r = 0.27; P = 0.008), total V&F (r = 0.25; P = 0.01), soyfoods (r = 0.28; P = 0.006), and dietary fiber (r = 0.36; P = 0.0003). Overall, urinary phytoestrogens (isoflavonoids + lignans) were significantly higher in "high" compared with "low" V&F consumers. Compared with the "low" V&F group, the "high" group consumed diets that were, on average, higher in fiber and carbohydrate and soyfoods and lower in fat; thus, the urinary phytoestrogens may also be a useful marker of healthier dietary patterns.

The spatial distribution of visual attention in hemineglect and extinction patients.

We studied the visual field distribution of speed and accuracy of manual responses to small brief light flashes, in patients with left hemineglect or extinction resulting from right hemisphere vascular lesions and in brain-damaged and healthy control subjects. All patients with right hemisphere lesions showed a greater impairment in both the speed of response and the detection rate in the contralesional than in the ipsilesional hemifield. This interfield difference increased with the eccentricity of stimulus presentation and was especially pronounced in neglect patients who showed a paradoxical increase in speed of response and detection rate at increasingly larger eccentricities in the ipsilesional hemifield. We hypothesize that both the contralesional slowing down and the ipsilesional speeding up of the response depends upon an exaggerated gradient of attention towards the ipsilesional hemifield. To assess whether these abnormalities concern automatic or controlled attentional processes, in a second experiment, we manipulated the predictability of the side of the stimulus presentation by using blocked rather than randomized stimulus presentations. This resulted in a speeding up of responses in both hemifields thus showing that the patients were able to focus attention to the side of stimulus presentation voluntarily. However, there was no modification of the contra-ipsilesional differences which, therefore, are likely to be related to abnormal automatic processes rather than controlled attention.

Consumption of exogenous bifidobacteria does not alter fecal bifidobacteria and breath hydrogen excretion in humans.

The hypothesis that consumption of bifidobacteria by humans would increase colonic bifidobacteria and decrease breath hydrogen excretion was examined. A commercially available strain of bifidobacteria was tracked through the gastrointestinal tract. We determined that a 12-d feeding period of 10(10) cells of exogenous bifidobacteria daily was adequate to achieve a stable number of exogenous bifidobacteria in the colon. A 12-d washout period was chosen because the exogenous bifidobacteria could no longer be detected at that time. A double-blind crossover study used both male and female subjects. The order of treatment with skim milk alone or skim milk + bifidobacteria was randomized. Breath hydrogen excretion (micromol/L) and fecal counts of total bifidobacteria [log colony forming units (CFU)/g feces] were not significantly different between males and females and were not affected by consumption of exogenous bifidobacteria. Calculations based on the numbers of exogenous bifidobacteria consumed and the fecal numbers of exogenous bifidobacteria excreted suggested that numbers of the exogenous strain increased within the gastrointestinal tract. These data suggest that it is difficult to permanently alter total colonic bifidobacteria and affect physiologic function (net hydrogen in the colon as reflected by breath hydrogen) by feeding bifidobacteria, although the percentage of the total bifidobacteria represented by the exogenous strain can be affected.

Paclitaxel plus ifosfamide in advanced ovarian cancer: a multicenter phase II study.

BACKGROUND: While ovarian cancer is one of the most sensitive cancers to cytotoxic drugs, with objective response rates of 60-80% routinely being reported in previously untreated patients, the majority of individuals with advanced disease ultimately relapse. Paclitaxel, a new and novel antimicrotubule agent, has shown activity as a salvage therapy in epithelial ovarian cancer. More importantly, in a prior study, it has been shown to be active in tumors that have displayed resistance to platinum compounds, with a reported response rate of 20%. Ifosfamide has shown activity in the treatment of patients who previously demonstrated clinical resistance to a platinum-cyclophosphamide combination. Recently, a synergistic activity of Taxol combined with ifosfamide has been reported in ovarian cell lines. Based on these data, a phase I/II study of a combination treatment with paclitaxel and ifosfamide was performed. PATIENTS AND METHODS: Thirty-one patients with recurrent ovarian cancer or ovarian cancer refractory to cisplatin (CDDP)-containing regimens were treated with paclitaxel at a dose of 135 mg/m2 on day 1; ifosfamide was administered at 1 g/m2 on days 2 and 3 for the first cycle and 1.5 and 2 g/m2 with the same schedule in cycles 2 and 3, respectively. In the absence of toxicity, the dose of ifosfamide was maintained at 2 g/m2 for the last three cycles. Cytotoxic therapy was repeated every 3 weeks. RESULTS: A 30% overall objective response rate was achieved in the 30 patients assessable for response. Among 21 platinum-resistant patients, 4 partial responses (19%) were observed, while in the 9 platinum-sensitive patients 2 complete responses and 3 partial responses (55%) were observed. Myelosuppression was the predominant toxicity. Leukopenia (WHO grade 3-4) occurred in 10% of patients who received ifosfamide at a dose of 1 g/m2 and in 18% of patients treated with ifosfamide at 1.5 g/m2. CONCLUSION: Our results confirmed a low activity of paclitaxel in platinum-resistant patients. The results of this combination treatment with paclitaxel-ifosfamide in our platinum-sensitive patients support further investigations in a randomized study of the combination regimen against paclitaxel alone or retreatment with organoplatinum compounds.