Evaluation of the Antiproliferative Effects of Essiac™ on In Vitro and In Vivo Models of Prostate Cancer Compared to Paclitaxel

Essiac?, a widely consumed, sparsely tested herbal tea, was evaluated for preparation consistency and antiproliferative effects on prostate cancer cells and xenografts. High performance liquid chromatography (HPLC) was used to compare different lots of Essiac and evaluate extraction consistency by comparing peak areas in concentrated preparations. Repeated analysis of one lot showed < 2% RSD between corresponding peaks. Absolute peak areas varied widely between lots, but similarity in relative size of corresponding peaks was observed. Cytotoxic effects of Essiac were tested in vitro by crystal violet assay and analysis of cell cycle distribution by flow cytometry, but no differences between control and treatment groups was observed. Paclitaxel was used as a positive control in cell cycle analysis and was the only treatment which showed significant effects on cell cycle distribution. Toxicity in nude mice was tested, and efficacy in inhibiting PC-3 xenograft growth. No toxicity or tumour size difference was observed dosing up to 240 mg/kg QD, over 28 days, excepting the positive control group treated with paclitaxel. Ki-67 and PCNA expression was analyzed in treated tumors, but no difference in expression of either marker was observed. These evaluations suggest Essiac has no marked antiproliferative effect on the models tested.     

Fate and effects of the insecticide Dursban® 4E in indoor Elodea-dominated and macrophyte-free freshwater model ecosystems: I. Fate and primary effects of the active ingredient chlorpyrifos

The fate of the insecticide Dursban^® 4E (active ingredient chlorpyrifos) and its effect on crustaceans and insects was studied in indoor experimental freshwater ecosystems that intended to mimick drainage ditches. A single dose (simulating aerial drift) was applied to achieve nominal chlorpyrifos concentrations of 5 or 35 g/L. Two experiments were performed, one in which all model ecosystems were dominated by the macrophyte Elodea nuttallii, and one using systems devoid of macrophytes.In macrophyte-dominated systems, Elodea vegetation adsorbed a large proportion of the dose applied and hampered the mixing of the insecticide in the water (at least up till day 8). Only a small proportion became incorporated in the sediment. In open water systems the insecticide was rapidly mixed in the water, and the sediment played a very significant role as sink for chlorpyrifos. In both Elodea-dominated and open water systems 50% of the dose applied had disappeared on day 8 post-treatment. The rate of disappearance of chlorpyrifos was relatively rapid in water and macrophytes, and relatively slow in the sediment.Of the arthropods in the zooplankton Cladocera were more susceptible than Copepoda. Significant effects (p0.05) on Cladocera occurred relatively late in Elodea-dominated systems (in week 4 post-application) in contrast to open water systems (week 1), which is in accordance with the observed differences in the fate of chlorpyrifos. Daphnia pulex, D. longispina and Simocephalus vetulus recovered in the model ecosystems when chlorpyrifos concentrations were lower than 0.1–0.2 g/L, which is in agreement with results of laboratory protocol tests performed with these cladocerans.Among the macroscopic Arthropoda the apparent order of susceptibility was amphipods > insects > isopods. The isopod Asellus aquaticus was more sensitive to the application of the insecticide than the closely related species Proasellus coxalis. In treated open water systems the latter even increased significantly in numbers. Cage experiments in the model ecosystems performed with several species of Arthropoda indicate that laboratory protocol tests may give a reasonable prediction of short-term direct effects of chlorpyrifos for the same species inhabiting more complex aquatic systems.     

The sound of operation and the acoustic attenuation of the Ohmeda Medical Giraffe OmniBed™

The neonatal intensive care unit (NICU) is an environment that provides premature and fragile infants with health provisions needed to make a complete recovery. Premature infants are often born before their auditory systems have had an opportunity to fully mature. Research has shown that the ambient acoustic environment in the NICU exceeds the maximum noise level recommended by the American Academy of Pediatrics, even after measures have been taken to decrease noise levels. The purpose of this study is to evaluate noise levels inside an Ohmeda Medical Giraffe? OmniBed?, the natural attenuation of the incubator, and the effects of modifications on attenuation and reverberation within the Giraffe TM OmniBed?. The normal operation of the Giraffe? OmniBed? is 41.7 dBA which indicates a lower noise of operation than previous studies. The Giraffe? OmniBed? naturally attenuates 12 dBA. Leaving an access latch or portal door open causes a statistically significant (P=.001) increase in sound within the bassinet. All modifications in the no-noise and the noise conditions showed a statistically significant (P=.001) drop in L(eq) when compared to baseline.     

The effects of music and movement on mother–infant interactions

Two experiments investigated the effects of a music and movement (M&M) programme on healthy first-time mothers and their 2–6-month-old infants over a five-week period. Experiment 1 (N?=?96) examined the effects of the M&M activities and the face-to-face (F2F) social contact of a group instruction method on the perception of mothers' interactions with their infants and maternal postnatal attachment. Generally, M&M increased mothers' interactions with their infants specific to music-type activities and mothers' attachment to their infants. Contrary results occurred for No M&M-control group mothers. The presence/absence of F2F had no effect. Experiment 2 (N?=?44) focused on behavioural effects of M&M on mothers' infant-directed speech (IDS) and mother–infant reciprocity. M&M increased dyadic reciprocity, and increased the duration, mean pitch and pitch range of mothers' IDS. Without M&M a decrease in attentional characteristics of mothers' IDS and dyadic reciprocity occurred.     

Effect of GonaCon™ vaccine on black-tailed prairie dogs: immune response and health effects

Management of prairie dogs in the past has included poisoning, fumigants, barriers, and relocation. Because of the diverse attitudes related to prairie dog management, nonlethal methods that allow the existence of prairie dogs but help minimize damage related to population growth need to be developed. GonaCon™ is an immunocontraceptive vaccine that elicits antibodies to native GnRH; this prevents the secretion of reproductive hormones necessary for sperm and oocyte production. Prairie dogs were vaccinated with 0.1, 0.2, or 0.4 mL of the GonaCon™ emulsion intramuscularly in the upper thigh containing 100, 200, or 400 μg GnRH conjugate, respectively. Control animals were vaccinated with 0.4 mL saline emulsion in the upper thigh. Blood samples (≤1 mL) were taken from the femoral vein once pretreatment and at 1, 2, 3, 4, 6, and 15 months post-vaccination. Age (adult or juvenile) did not affect immune response to GonaCon™. Antibody titers were higher in the 200 and 400 μL GonaCon™ groups than in the 100 μL group, and there was no difference between the 200 and 400 μL GonaCon™ groups. No adverse effects of GonaCon™ were noted on weight or blood chemistry parameters during the study. GonaCon™ will likely contracept prairie dogs for ≥1 year in the field using either 200 or 400 μg conjugate. GonaCon™ could be incorporated into management plans to help maintain prairie dog populations while reducing habitat degradation due to overpopulation.     

The effects of ‘activating’ almonds on consumer acceptance and gastrointestinal tolerance

Purpose

Recommendations to soak nuts prior to consumption to reduce phytate concentrations and improve gastrointestinal tolerance have received much attention in the popular press. This is despite no supporting scientific evidence for the practice. There is also a lack of information about how soaking nuts might affect consumer acceptability. This study primarily assessed the effects of soaking almonds on consumer acceptance and secondly assessed effects on gastrointestinal tolerance.

Methods

In this 8-week randomised crossover trial, 76 participants were allocated in balanced order to receive 30 g/day of four different preparations of almonds for 12 days: whole unsoaked, whole soaked, sliced unsoaked, and sliced soaked. Ratings of overall liking, desire to consume, and likelihood of future consumption, and severity of gastrointestinal symptoms were measured daily on visual analogue scales. The phytate concentrations were measured in all four nut types using high-performance liquid chromatography.

Results

Mean acceptance ratings of all nut types were above the neutral point indicating they were acceptable. However, sliced soaked almonds were rated significantly lower overall for all three acceptance scales compared to the other treatments (all P ≤ 0.003). The sliced unsoaked almonds were rated lower than both whole nut treatments (all P ≤ 0.006), while there were no significant differences between the two whole nut treatments (all P ≥ 0.511). Gastrointestinal symptoms were minimal, but flatulence was rated significantly higher for all time points combined for soaked whole nuts compared to unsoaked whole nuts (P = 0.005). Compared to the whole unsoaked nuts (mean [SD] 531 [9] mg/100 g), phytate concentration was higher for the whole soaked almonds (563 [38] mg/100 g, P = 0.016), with no evidence of a difference for the sliced soaked almonds (548 [27] mg/100 g, P = 0.197) and no difference between the soaked forms (P = 0.262).

Conclusions

This research supports previous results suggesting nuts, including different forms, are an acceptable food. They are also well tolerated gastrointestinally, but soaking does not improve gastrointestinal tolerance or acceptance as claimed in the lay literature.

     

Fate and effects of the insecticide Dursban® 4E in indoor Elodea-dominated and macrophyte-free freshwater model ecosystems: III. Aspects of ecosystem functioning

The effects of the insecticide Dursban^® 4E (active ingredient chlorpyrifos) on aspects of water chemistry, community metabolism, and decomposition of particulate organic matter were studied in indoor freshwater microcosms intended to mimic drainage ditches. To several of these systems, a single dose (simulating aerial drift) was applied to achieve nominal chlorpyrifos concentrations of 5 or 35 g/L. Two experiments were performed; one, in which all model ecosystems were dominated by the macrophyte Elodea nuttallii, and one, using systems devoid of macrophytes. The response of ecosystem functioning is discussed in relation to the shifts in community structure observed.Treatment effects on community metabolism, as signaled by a decrease in dissolved oxygen and pH and an increase in alkalinity and conductivity, could be observed in the high-dose Elodea-dominated microcosms only. In addition, Dursban 4E application in these systems resulted in a more persistent decrease in the decay rate of macrophyte material present in litter bags than in open water microcosms. Concentrations of inorganic nitrogen and orthophosphate in the water column of both types of model ecosystem were hardly affected by insecticide application. It is concluded that the impact of Dursban 4E on ecosystem functioning differed considerably between the two types of model ecosystems, and that functional endpoints were more robust than structural properties.     

The effects of developmental placement on young children's cognitive and social‐emotional development

The relationship between developmental placement as a result of preschool and kindergarten developmental testing and children's later cognitive achievement and social‐emotional growth was examined. Two hundred twenty‐three children were coded as Traditional, Overplaced, or “Buy a Year” depending on their scores on the Gesell Screening Test and the subsequent school placement. Their performancs on the full Gesell Developmental Test, 3rd grade New York State PEP Tests in reading and math, the Otis Lennon Mental Ability Test, and the Stanford Achievement Test (SAT) were compared. Those children who scored as immature on the Gesell Screening Test and who were retained a year according to the Gesell Developmental Placement Program, had the lowest scores on all measures even though they were almost a year older than the other two groups of children at the time of the PEP and SAT testing. In addition, referrals for special services and counselling were examined and there were no significant differences between the number of children referred from each Gesell status group in many areas, although more BAY children were referred to adaptive motor or resource programs. Other school related factors are also examined. Implications of this study on developmental placement are discussed.     

The effects of weight and waist change on the risk of long-term mortality in older adults- The Bambuí (Brazil) Cohort Study of Aging

Objective

We aimed to investigate the risk of long-term mortality associated with weight and waist circumference (WC) change among older adults, particularly the overweight and obese ones.

Design

Cohort Study.

Setting

The Bambuí (Brazil) Cohort Study of Aging.

Participants

Community-dwelling elderly (n=1138).

Measurements

Weight and WC were reassessed three years after baseline. Mortality risk associated with a 5% weight/WC loss and gain was compared to that of weight/WC stability by Cox models adjusted for clinical, behavioral and social known risk factors for death (age, gender, BMI, smoking, diabetes, total cholesterol, hypertension, Chagas disease, major electrocardiographic changes, physical activity, B-type natriuretic peptide, C-reactive protein, creatinine, education and household income).

Results

Female sex was predominant (718; 63.1%). Mean age was 68 (6.7) years. Weight stability (696; 61.1%) was more common than weight loss (251; 22.1%) or gain (191; 16.8%). WC remained stable in 422 (37.3%), decreased in 418 (37.0%) and increased in 291 (25.7%) participants. There were 334 (29.3%) deaths over a median follow-up time of 8.0 (6.4-8.0) years from weight/WC reassessment. Weight loss (HR 1.69; 95% CI 1.30-2.21) and gain (HR 1.37; 95% CI 1.01-1.85) were associated with increased mortality, except in those who were physically active in which weight gain was associated with decreased mortality. Results were similar for participants who were overweight/ obese or with abdominal obesity at baseline (HR 1.41; 95%CI 1.02-1.97 and HR 2.01; 95%CI 1.29-3.12, for weight loss and gain, respectively). WC change was not significantly associated with mortality.

Conclusion

Although weight loss has been recommended for adults with excessive weight regardless of age, weight change might be detrimental in older adults. Rather than weight loss, clinical interventions should target healthy lifestyle behaviors that contribute to weight stability, particularly physical activity in overweight and obese older adults.

     

Synergistic effects of Aroclor® 1254 and mirex on the semen characteristics of American Kestrels

Semen characteristics of captive American Kestrels (Falco sparverius) fed 8 ppm mirex or 33 ppm Aroclor^® 1254, singly or in combination, were compared to a control group. Aroclor^® 1254 produced a decline in sperm concentration but no compensatory increase in semen volume, resulting in a 22–27% decrease in sperm numbers per ejaculate. Mirex produced a marked decline in sperm concentration with a slight compensatory increase in semen volume resulting in a 70% decrease in sperm numbers. The combination of Aroclor^® 1254 and mirex, at the same concentrations as fed singly, decreased sperm concentration to the same level as the Aroclor^® alone with a 73% increase in semen volume, resulting in sperm numbers which did not differ from those of the controls. No effect on sperm motility was observed for any contaminant. Temporal patterns in semen characteristics differed. There was a highly significant interaction effect between Aroclor^® 1254 and mirex. The excretion of mirex was increased in the presence of Aroclor^® 1254, and the combination diet reduced the relative concentration of Aroclor^® in the testes. The testicular mass of the PCBs + mirex group was increased. The results suggest that migratory flesheating birds feeding on a PCB- or mirex-contaminated food chain could consume enough toxicant to alter their semen quality in that breeding season, which, when coupled with altered courtship, could reduce the fertility of eggs and the reproductive fitness of the individual.     

“I am Your Mother and Your Father!” In Vitro Derived Gametes and the Ethics of Solo Reproduction

In this paper, we will discuss the prospect of human reproduction achieved with gametes originating from only one person. According to statements by a minority of scientists working on the generation of gametes in vitro, it may become possible to create eggs from men’s non-reproductive cells and sperm from women’s. This would enable, at least in principle, the creation of an embryo from cells obtained from only one individual: ‘solo reproduction’. We will consider what might motivate people to reproduce in this way, and the implications that solo reproduction might have for ethics and policy. We suggest that such an innovation is unlikely to revolutionise reproduction and parenting. Indeed, in some respects it is less revolutionary than in vitro fertilisation as a whole. Furthermore, we show that solo reproduction with in vitro created gametes is not necessarily any more ethically problematic than gamete donation—and probably less so. Where appropriate, we draw parallels with the debate surrounding reproductive cloning. We note that solo reproduction may serve to perpetuate reductive geneticised accounts of reproduction, and that this may indeed be ethically questionable. However, in this it is not unique among other technologies of assisted reproduction, many of which focus on genetic transmission. It is for this reason that a ban on solo reproduction might be inconsistent with continuing to permit other kinds of reproduction that also bear the potential to strengthen attachment to a geneticised account of reproduction. Our claim is that there are at least as good reasons to pursue research towards enabling solo reproduction, and eventually to introduce solo reproduction as an option for fertility treatment, as there are to do so for other infertility related purposes.     

The effects of price and policy on marijuana use: what can be learned from the Australian experience?

This research examines the responsiveness of the demand for marijuana to changes in its money price and criminal status using data on individuals from the Australian National Drug Strategy's Household Surveys (NDSHS). The results suggest that both the prevalence of marijuana use and the conditional demand for marijuana in the general population are responsive to changes in its money price. Significant differences are found in the effect of price on participation in marijuana use across age-groups, with participation by youth more price sensitive than participation by older age-groups. Similarly, the effect of the legal status of marijuana use on the participation decision is found to differ across age-groups and gender. Specifically, decriminalisation is associated with an increases in the prevalence of use by males over the age of 25. There is no evidence that decriminalisation significantly increases participation in marijuana use by either young males or females, or that decriminalisation increases the frequency of use among marijuana users.     

In Vitro Effects of the Endocrine Disruptor p,p’-DDT on Human Follitropin Receptor

Background:

1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p′-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p′-DDT exposure and reproductive abnormalities.

Objectives:

To investigate the putative effects of p,p′-DDT on the human follitropin receptor (FSHR) function.

Methods

and Results: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p′-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p′-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p′-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p′-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p′-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p′-DDT was dependent on the FSHR. In addition, p,p′-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p′-DDT and potentiation of the FSHR response to FSH by p,p′-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p′-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p′-DDT and 16a into the FSHR transmembrane bundle.

Conclusion:

p,p′-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein–coupled receptors are additional targets of endocrine disruptors.

Citation:

Munier M, Grouleff J, Gourdin L, Fauchard M, Chantreau V, Henrion D, Coutant R, Schiøtt B, Chabbert M, Rodien P. 2016. In vitro effects of the endocrine disruptor p,p′-DDT on human follitropin receptor. Environ Health Perspect 124:991–999; http://dx.doi.org/10.1289/ehp.1510006     

Put “gender glasses” on the effects of phenolic compounds on cardiovascular function and diseases

Introduction

The influence of sex and gender is particularly relevant in cardiovascular diseases (CVD) as well as in several aspects of drug pharmacodynamics and pharmacokinetics. Anatomical and physiological differences between the sexes may influence the activity of many drugs, including the possibility of their interaction with other drugs, bioactive compounds, foods and beverages. Phenolic compounds could interact with our organism at organ, cellular, and molecular levels triggering a preventive action against chronic diseases, including CVD.

Results

This article will review the role of sex on the activity of these bioactive molecules, considering the existence of sex differences in oxidative stress. It describes the pharmacokinetics of phenolic compounds, their effects on vessels, on cardiovascular system, and during development, including the role of nuclear receptors and microbiota.

Conclusions

Although there is a large gap between the knowledge of the sex differences in the phenolic compounds’ activity and safety, and the urgent need for more research, available data underlie the possibility that plant-derived phenolic compounds could differently influence the health of male and female subjects.

     

The effects of socioeconomic diversity on the language,cognitive and social–emotional development of children from low‐income backgrounds

Previous studies on the influence of mixed groupings within preschool classrooms have indicated positive effects on children’s development. This study extended earlier findings to determine the effects of socioeconomic diversity within the classroom on the language, cognitive and social–emotional development of preschool children of low‐income backgrounds. Twenty‐seven preschool children were enrolled in two classrooms in a private university’s child development center. Twenty of the 27 enrolled were from low‐income backgrounds. The children were tested to determine a baseline measure of their language, cognitive and social–emotional skills. Classroom observations of the children’s language behavior were coded. Post‐testing was done at the conclusion of the school year to determine growth in language, cognitive and social–emotional skills. Differences in language usage and social–emotional development were observed. These results suggest that mixed income grouping as well as teacher interactions influence language and social–emotional development of children from low‐income backgrounds.