Effects In Mammals Research Articles

Chemicals having estrogenic activity can be released from some bisphenol A-free, hard and clear, thermoplastic resins.

BackgroundChemicals that have estrogenic activity (EA) can potentially cause adverse health effects in mammals including humans, sometimes at low doses in fetal through juvenile stages with effects detected in adults. Polycarbonate (PC) thermoplastic resins made from bisphenol A (BPA), a chemical that has EA, are now often avoided in products used by babies. Other BPA-free thermoplastic resins, some hypothesized or advertised to be EA-free, are replacing PC resins used to make reusable hard and clear thermoplastic products such as baby bottles.MethodsWe used two very sensitive and accurate in vitro assays (MCF-7 and BG1Luc human cell lines) to quantify the EA of chemicals leached into ethanol or water/saline extracts of fourteen unstressed or stressed (autoclaving, microwaving, UV radiation) thermoplastic resins. Estrogen receptor (ER)-dependent agonist responses were confirmed by their inhibition with the ER antagonist ICI 182,780.ResultsOur data showed that some (4/14) unstressed and stressed BPA-free thermoplastic resins leached chemicals having significant levels of EA, including one polystyrene (PS), and three Tritan™ resins, the latter reportedly EA-free. Exposure to UV radiation in natural sunlight resulted in an increased release of EA from Tritan™ resins. Triphenyl-phosphate (TPP), an additive used to manufacture some thermoplastic resins such as Tritan™, exhibited EA in both MCF-7 and BG1Luc assays. Ten unstressed or stressed glycol-modified polyethylene terephthalate (PETG), cyclic olefin polymer (COP) or copolymer (COC) thermoplastic resins did not release chemicals with detectable EA under any test condition.ConclusionsThis hazard survey study assessed the release of chemicals exhibiting EA as detected by two sensitive, widely used and accepted, human cell line in vitro assays. Four PC replacement resins (Tritan™ and PS) released chemicals having EA. However, ten other PC-replacement resins did not leach chemicals having EA (EA-free-resins). These results indicate that PC-replacement plastic products could be made from EA-free resins (if appropriate EA-free additives are chosen) that maintain advantages of re-usable plastic items (price, weight, shatter resistance) without releasing chemicals having EA that potentially produce adverse health effects on current or future generations.

A 28-day oral toxicity evaluation of small interfering RNAs and a long double-stranded RNA targeting vacuolar ATPase in mice

New biotechnology-derived crop traits have been developed utilizing the natural process of RNA interference (RNAi). However, plant-produced double stranded RNAs (dsRNAs) are not known to present a hazard to mammals because numerous biological barriers limit uptake and potential for activity. To evaluate this experimentally, dsRNA sequences matching the mouse vATPase gene (an established target for control of corn rootworms) were evaluated in a 28-day toxicity study with mice. Test groups were orally gavaged with escalating doses of either a pool of four 21-mer vATPase small interfering RNAs (siRNAs) or a 218-base pair vATPase dsRNA. There were no treatment-related effects on body weight, food consumption, clinical observations, clinical chemistry, hematology, gross pathology, or histopathology endpoints. The highest dose levels tested were considered to be the no observed adverse effect levels (NOAELs) for the 21-mer siRNAs (48mg/kg/day) and the 218bp dsRNA (64mg/kg/day). As an additional exploratory endpoint, vATPase gene expression, was evaluated in selected gastrointestinal tract and systemic tissues. The results of this assay did not indicate treatment-related suppression of vATPase. The results of this study indicate that orally ingested dsRNAs, even those targeting a gene in the test species, do not produce adverse health effects in mammals.

Melatonin in sperm biology: breaking paradigms.

Melatonin is a ubiquitous molecule, present in a wide range of organisms, and involved in multiple functions. Melatonin relays the information about the photoperiod to the tissues that express melatonin-binding sites in both central and peripheral nervous systems. This hormone has a complex mechanism of action. It can cross the cell plasma membrane and exert its actions in all cells of the body. Certain melatonin actions are mediated by receptors that belong to the superfamily of G-protein-coupled receptors (GPCRs), the MT1 and MT2 membrane. Melatonin can also bind to calmodulin as well as to nuclear receptors of the retinoic acid receptor family, RORα1, RORα2 and RZRβ. The purpose of this review is to report on recent developments in the physiological role of melatonin and its receptors. Specific issues concerning the biological function of melatonin in mammalian seasonal reproduction and spermatozoa are considered. The significance of the continuous presence of melatonin in seminal plasma with a fairly constant concentration is also discussed.

Paternal influences on offspring development: behavioural and epigenetic pathways.

Although mammalian parent-offspring interactions during early life are primarily through the mother, there is increasing evidence for the impact of fathers on offspring development. A critical issue concerns the pathways through which this paternal influence is achieved. In the present review, we highlight the literature suggesting several of these routes of paternal effects in mammals. First, similar to mothers, fathers can influence offspring development through the direct care of offspring, as has been observed in biparental species. Second, there is growing evidence that, even in the absence of contact with offspring, fathers can transmit environmentally-induced effects (i.e. behavioural, neurobiological and metabolic phenotypes induced by stress, nutrition and toxins) to offspring and it has been speculated that these effects are achieved through inherited epigenetic variation within the patriline. Third, fathers may also impact the quality of mother-infant interactions and thus achieve an indirect influence on offspring. Importantly, these pathways of paternal influence are not mutually exclusive but rather serve as an illustration of the complex mechanisms through which parental influence is achieved. These influences may serve to transmit traits across generations, thus leading to a transgenerational transmission of neurobiological and behavioural phenotypes.

Developmental exposure to the polybrominated diphenyl ether PBDE 209: Neurobehavioural and neuroprotein analysis in adult male and female mice

Polybrominated diphenyl ethers (PBDEs), used as flame retardants in polymer products, are reported to cause developmental neurotoxic effects in mammals. The present study have investigated neurotoxic effects arising from neonatal exposure to PBDE 209, including alterations in sex differences, spontaneous behaviour, learning and memory, neuroproteins and altered susceptibility of the cholinergic system in adults.Three-day-old NMRI mice, of both sexes, were exposed to PBDE 209 (2,2′,3,3′,4,4′,5,5′,6,6′-decaBDE at 0, 1.4, 6.0 and 14.0μmol/kg b.w.). At adult age (2–7 months) a similar developmental neurotoxic effects in both male and female mice were seen, including lack of or reduced habituation to a novel home environment, learning and memory defects, modified response to the cholinergic agent's paraoxon (males) and nicotine (females) indicating increased susceptibility of the cholinergic system. The behavioural defects were dose–response related and persistent. In mice of both sexes and showing behavioural defects, neuroprotein tau was increased.

Invertebrate extracellular phagocyte traps show that chromatin is an ancient defence weapon.

Controlled release of chromatin from the nuclei of inflammatory cells is a process that entraps and kills microorganisms in the extracellular environment. Now termed ETosis, it is important for innate immunity in vertebrates. Paradoxically, however, in mammals, it can also contribute to certain pathologies. Here we show that ETosis occurs in several invertebrate species, including, remarkably, an acoelomate. Our findings reveal that the phenomenon is primordial and predates the evolution of the coelom. In invertebrates, the released chromatin participates in defence not only by ensnaring microorganisms and externalizing antibacterial histones together with other haemocyte-derived defence factors, but crucially, also provides the scaffold on which intact haemocytes assemble during encapsulation; a response that sequesters and kills potential pathogens infecting the body cavity. This insight into the early origin of ETosis identifies it as a very ancient process that helps explain some of its detrimental effects in mammals.

Gestational and lactational exposure to the polychlorinated biphenyl mixture Aroclor 1254 modulates retinoid homeostasis in rat offspring

Polychlorinated biphenyls (PCBs) induce a broad spectrum of biochemical and toxic effects in mammals including alterations of the vital retinoid (vitamin A) system. The aim of this study was to characterize alterations of tissue retinoid levels in rat offspring and their dams following gestational and lactational exposure to the PCB mixture Aroclor 1254 (A1254) and to assess the interrelationship of these changes with other established sensitive biochemical and toxicological endpoints. Sprague-Dawley rat dams were exposed orally to 0 or 15mg/kg body weight/day of A1254 from gestational day 1 to postnatal day (PND) 23. Livers, kidneys and serum were collected from the offspring on PNDs 35, 77 and 350. Tissue and serum retinoid levels, hepatic cytochrome P450 (CYP) enzymes and serum thyroid hormones were analyzed. A multivariate regression between A1254 treatment, hepatic retinoid levels, hepatic CYP enzymes activities, thyroid hormone levels and body/liver weights was performed using an orthogonal partial least-squares (PLS) analysis. The contribution of dioxin-like (DL) components of A1254 to the observed effects was also estimated using the toxic equivalency (TEQ) concept. In both male and female offspring short-term alterations in tissue retinoid levels occurred at PND35, i.e. decreased levels of hepatic retinol and retinoic acid (RA) metabolite 9-cis-4-oxo-13,14-dihydro-RA with concurrent increases in hepatic and renal all-trans-RA levels. Long-term changes consisted of decreased hepatic retinyl palmitate and increased renal retinol levels that were apparent until PND350. Retinoid system alterations were associated with altered CYP enzyme activities and serum thyroid hormone levels as well as body and liver weights in both offspring and dams. The estimated DL activity was within an order of magnitude of the theoretical TEQ for different endpoints, indicating significant involvement of DL congeners in the observed effects. This study shows that tissue retinoid levels are affected both short- and long-term by developmental A1254 exposure and are associated with alterations of other established endpoints of toxicological concern.

Estrogenic chemicals often leach from BPA-free plastic products that are replacements for BPA-containing polycarbonate products.

BackgroundXenobiotic chemicals with estrogenic activity (EA), such as bisphenol A (BPA), have been reported to have potential adverse health effects in mammals, including humans, especially in fetal and infant stages. Concerns about safety have caused many manufacturers to use alternatives to polycarbonate (PC) resins to make hard and clear, reusable, plastic products that do not leach BPA. However, no study has focused on whether such BPA-free PC-replacement products, chosen for their perceived higher safety, especially for babies, also release other chemicals that have EA.MethodsWe used two, well-established, mammalian cell-based, assays (MCF-7 and BG1Luc) to assess the EA of chemicals that leached into over 1000 saline or ethanol extracts of 50 unstressed or stressed (autoclaving, microwaving, and UV radiation) BPA-free PC-replacement products. An EA antagonist, ICI 182,780, was used to confirm that agonist activity in leachates was due to chemicals that activated the mammalian estrogen receptor.ResultsMany unstressed and stressed, PC-replacement-products made from acrylic, polystyrene, polyethersulfone, and Tritan™ resins leached chemicals with EA, including products made for use by babies. Exposure to various forms of UV radiation often increased the leaching of chemicals with EA. In contrast, some BPA-free PC-replacement products made from glycol-modified polyethylene terephthalate or cyclic olefin polymer or co-polymer resins did not release chemicals with detectable EA under any conditions tested.ConclusionsThis hazard assessment survey showed that many BPA-free PC- replacement products still leached chemicals having significant levels of EA, as did BPA-containing PC counterparts they were meant to replace. That is, BPA-free did not mean EA-free. However, this study also showed that some PC-replacement products did not leach chemicals having significant levels of EA. That is, EA-free PC-replacement products could be made in commercial quantities at prices that compete with PC-replacement products that were not BPA-free. Since plastic products often have advantages (price, weight, shatter-resistance, etc.) compared to other materials such as steel or glass, it is not necessary to forgo those advantages to avoid release into foodstuffs or the environment of chemicals having EA that may have potential adverse effects on our health or the health of future generations.

Quinoa seeds leach phytoecdysteroids and other compounds with anti-diabetic properties

Quinoa (Chenopodium quinoa Willd.) contains high levels of biologically active phytoecdysteroids, which have been implicated in plant defense from insects, and have shown a range of beneficial pharmacological effects in mammals. We demonstrated that the most prevalent phytoecdysteroid, 20-hydroxyecdysone (20HE), was secreted (leached) from intact quinoa seeds into water during the initial stages of seed germination. Leaching efficiency was optimized by ethanol concentration (70% ethanol), temperature (80°C), time (4h), and solvent ratio (5ml/g seed). When compared to extraction of macerated seeds, the leaching procedure released essentially all the 20HE available in the seeds (491μg/g seed). The optimized quinoa leachate (QL), containing 0.86% 20HE, 1.00% total phytoecdysteroids, 2.59% flavonoid glycosides, 11.9% oil, and 20.4% protein, significantly lowered fasting blood glucose in obese, hyperglycemic mice. Leaching effectively releases and concentrates bioactive phytochemicals from quinoa seeds, providing an efficient means to produce a food-grade mixture that may be useful for anti-diabetic applications.

Identification of an Olfactory Signal Molecule that Activates the Central Regulator of Reproduction in Goats

Pheromone signals regulate conspecific behavior and physiology [1]. Releaser pheromones induce specific behavior by exerting acute effects on the neuronal response, whereas primer pheromones induce physiological changes with long-lasting effects by changing the neuroendocrine status of the recipients. In mammals, although several types of releaser pheromones have been identified [2-5], the identities of primer pheromones, as well as their mechanisms of action, remain largely unknown [6]. In sheep and goats, the seasonally anestrous endocrine state of females is changed to the estrous state upon exposure to male scents [7, 8]. This so-called "male effect" is one of the most conspicuous primer pheromone effects in mammals [9, 10]. In this study, we have identified an olfactory signal molecule that activates the central regulator of reproduction, the gonadotropin-releasing hormone (GnRH) pulse generator, in goats. Using gas chromatography-mass spectrometry to analyze male goat headspace volatiles, we identified several ethyl-branched aldehydes and ketones. We electrophysiologically demonstrated that one of these compounds, 4-ethyloctanal, activates the GnRH pulse generator in female goats. This is the first report of an olfactory molecule that has been shown to activate the central reproductive axis, and this discovery will provide a new direction for primer pheromone research.

Perinatal exposure to perfluorooctane sulfonate affects glucose metabolism in adult offspring.

Perfluoroalkyl acids (PFAAs) are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS) is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0) were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21). To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders.

Diversity of Adjustments to Reward Downshifts in Vertebrates

This review focuses on reward-schedule effects, a family of learning phenomena involving surprising devaluations in reward quality or quantity (as in incentive contrast), and reward omissions (as in appetitive extinction), as studied in three taxonomic groups of vertebrates: mammals, birds, and amphibians. The largest database of dependable data comes from research with mammals in general, and with rats in particular. These experiments show a variety of behavioral adjustments to situations involving reward downshifts. For example, rats show disruption of instrumental and consummatory behavior directed at a small reward after receiving a substantially larger reward (called successive negative contrast, SNC)—a reward-schedule effect. However, instrumental SNC does not seem to occur when animals work for sucrose solutions—a reversed reward-schedule effect. Similar modes of adjustment have been reported in analogous experiments with avian and amphibian species. A review of the evidence suggests that carry-over signals across successive trials can acquire control over behavior under massed practice, but emotional memory is required to account for reward-schedule effects observed under widely spaced practice. There is evidence for an emotional component to reward-schedule effects in mammals, but similar evidence for other vertebrates is scanty and inconsistent. Progress in the comparative analysis of reward-schedule effects will require the intense study of a set of selected species, in selected reward-downshift situations, and aiming at identifying underlying neural mechanisms.

Short-Term Administration of Alibernet Red Wine Extract Failed To Affect Blood Pressure and To Improve Endothelial Function in Young Normotensive and Spontaneously Hypertensive Rats

As wine polyphenols were shown to possess many positive effects in mammals, including improvement of vascular function, this study investigated the effect of the Slovak Alibernet red wine extract (AWE) on blood pressure and vascular function in young normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Six weeks old, male, WKY and SHR were treated with AWE for three weeks at the dose of 24.2 mg/kg/day. Blood pressure (BP), determined by tail-cuff plethysmography, was significantly elevated in SHR vs. WKY and AWE failed to affect it. Lipid peroxidation was evaluated by determination of thiobarbituric acid-reactive substances. Vascular function was assessed in rings of the femoral artery using Mulvany-Halpern's myograph. Maximal endothelium-dependent acetylcholine (ACh)-induced relaxation was reduced in control SHR vs. WKY rats by approximately 9.3 %, which was associated with a significant decrease of its NO-independent component. AWE failed to affect maximal ACh-induced relaxation, both its NO-dependent and independent components, compared to controls of the same genotype. AWE however reduced lipid peroxidation in the left ventricle of both WKY and SHR and in the liver of SHR. In conclusion, three-week administration of AWE failed to reduce BP and to improve endothelial function in the femoral arteries of both genotypes investigated.

Haploid genomes illustrate epigenetic constraints and gene dosage effects in mammals

Sequencing projects have revealed the information of many animal genomes and thereby enabled the exploration of genome evolution. Insights into how genomes have been repeatedly modified provide a basis for understanding evolutionary innovation and the ever increasing complexity of animal developmental programs. Animal genomes are diploid in most cases, suggesting that redundant information in two copies of the genome increases evolutionary fitness. Genomes are well adapted to a diploid state. Changes of ploidy can be accommodated early in development but they rarely permit successful development into adulthood. In mammals, epigenetic mechanisms including imprinting and X inactivation restrict haploid development. These restrictions are relaxed in an early phase of development suggesting that dosage regulation appears less critical. Here we review the recent literature on haploid genomes and dosage effects and try to embed recent findings in an evolutionary perspective.

From Complex Behavior to New Drugs: Chemoinformatics Shows the Way

​IfIf you are a medicinal chemist casting your net for new drugs, you have a choice: you can take a bottom-up approach, in which you begin with a molecule that hits a known molecular target and hope it translates eventually into a physiological effect; or you can take a top-down approach, in which you begin with a molecule that causes the desired physiological effect and then find the molecular target in order to better understand the effect and optimize your drug's interaction with it. A computational approach to target identification is applied to elucidate the pharmacological targets underlying the regulation of feeding behavior in the nematode C. elegans. This top-down approach, called a phenotypic screen, seems to be the most practical route when you want to alter a complex behavior, such as feeding, which involves multiple tissues and unknown molecular pathways. But after finding the right molecule, discovering the target it hits and the pathway it affects can be challenging. Additionally, these discovery steps are by necessity performed in a lab model, and the targets and pathways in the model must still be shown to be relevant to human physiology. In a new study in this issue of PLOS Biology, George Lemieux, Bryan Roth, Brian Shoichet, Kaveh Ashrafi, and colleagues analyze a set of compounds emerging from a phenotypic screen of fat content in worms. By combining chemoinformatics, in vitro testing, and in vivo assays, they identify previously unknown pathways that affect feeding behavior in worms and that are likely to have important effects in mammals. The authors began with a set of 84 compounds they had found altered fat metabolism in the worm. For all but one of these compounds, no biological targets were known. To find likely targets, they interrogated a database of almost 2,500 targets and more than 8 million ligand interactions with mostly mammalian targets, comparing the structure of their compounds with ligand sets in the database. They found possible targets for 79 of the 84 compounds, and chose 16 compounds for in vitro testing against the predicted mammalian targets, many of which were enzymes or membrane receptors. Next, they returned to worms. In the original screen, fat accumulation (assayed by fluorescence microscopy) stood in for feeding. Here, they measured the rate of contraction of the pharynx—swallowing, essentially—for a more direct indication of the related physiology of feeding behavior. Four compounds stood out for their ability to increase feeding in larvae and adults. But did these four do so through interacting with worm counterparts of mammalian targets that were identified? To find out, the authors knocked down the predicted target using RNA interference. They reasoned that if the compound interacted with the predicted target, its effect was almost certainly inhibitory (virtually all drugs inhibit, rather than facilitate, action of the biomolecules they interact with). Therefore, knocking down the predicted target should have the same effect as the compound, and furthermore, adding the compound shouldn't increase the effect, since the target would already be out of commission. According to database predictions and in vitro testing, the compound D20 inhibited a human receptor tyrosine kinase (RTK) called Flt-3. Worms have no exact match, but they do have many similar RTKs. Testing each of them without and then with D20, they found that one, called ver-3, increased feeding when knocked down but was insensitive to additional D20, indicating that D20 acted on ver-3. Using the same strategy, the authors also showed that another compound, called F15, acted on a receptor similar to human oxytocin receptor, which is known to influence feeding behavior in mammals. Further analysis identified two other pathways, for a total of four, all previously undescribed with respect to feeding regulation in the worm and all with relevance to vertebrate feeding regulation. It is not yet clear whether the pathways affect feeding behavior in humans. The strategy exploited in this study has wide applicability for discovering drugs for other behaviors, as long as a phenotypic correlate can be found and measured in an animal model. Not every compound identified will have a relevant human target, but if the success rate in future trials approximates that from this study, this method may prove to be a rich source of new compounds, targets, and pathways that can aid the design of the next generation of drugs for human use. Lemieux GA, Keiser MJ, Sassano MF, Laggner C, Mayer F, et al. (2013) In silico Molecular Comparisons of C. elegans and Mammalian Pharmacology Identify Distinct Targets that Regulate Feeding. doi:10.1371/journal.pbio.1001712

Indole diterpene alkaloids as novel inhibitors of the Wnt/β-catenin pathway in breast cancer cells

Penitrems are indole diterpene alkaloids best known for their BK channel inhibition and tremorgenic effects in mammals. In a previous study, penitrems A–F (1–5), their biosynthetic precursors, paspaline (6) and emindole SB (7), and two brominated penitrem analogs 8 and 9 demonstrated promising in vitro antiproliferative, antimigratory, and anti-invasive effects in the MTT (MCF-7 and MDA-MB-231), wound-healing, and Cultrex® BME cell invasion (MDA-MB-231) assays, respectively. The study herein reports the novel ability of penitrem A to suppress total β-catenin levels in MDA-MB-231 mammary cancer cells. Nine new penitrem analogs (10–18) were semisynthetically prepared, in an attempt to identify pharmacophores correlated with BK channel inhibition and tremorgenicity of penitrems and decrease their toxicity. The degree of BK channel inhibition was assessed using the nematode Caenorhabditis elegans, and in vivo tremorgenic EC50 was calculated using CD-1 male mice following an Up-and-Down Procedure (UDP). Although new analogs were generally less active than parent compound 1, some showed no BK channel inhibition or tremorgenicity and retained the ability of penitrem A (1) to suppress total β-catenin levels in MDA-MB-231 cells. Paspaline (6) and emindole SB (7), both lacking BK channel inhibition and tremorgenicity, represent the simplest indole diterpene skeleton that retains the antiproliferative, antimigratory and total β-catenin suppressing effects shown by the more complex penitrem A (1).

UČINKOVITOST BIOLOŠKI AKTIVNIH SASTAVNICA MATIČNE MLIJEČI: ANALIZA I STANDARDIZACIJA

Royal jelly is a viscous substance secreted by the hypopharyngeal and mandibular glands of worker honeybees (Apis mellifera) that contains a considerable amount of proteins, free amino acids, lipids, vitamins, sugars, and bioactive substances such as 10-hydroxy-trans-2-decenoic acid, antibacterial protein, and 350-kDa protein. These properties make it an attractive ingredient in various types of healthy foods. This article brings a brief review of the molecular mechanisms involved in the development of certain disorders that can be remedied by royal jelly, based on a selection of in vivo and in vitro studies. It also describes current understanding of the mechanisms and beneficial effects by which royal jelly helps to combat aging-related complications. Royal jelly has been reported to exhibit beneficial physiological and pharmacological effects in mammals, including vasodilative and hypotensive activities, antihypercholesterolemic activity, and antitumor activity. As its composition varies significantly (for both fresh and dehydrated samples), the article brings a few recommendations for defining new quality standards.

A Randomized Double Blind Placebo Controlled Evaluation of MSM for Exercise Induced Discomfort/Pain.

Methylsulfonylmethane (MSM) has been reported to provide anti‐inflammatory & antioxidant effects in mammals. Resistance exercise is known to induce both inflammation & oxidative stress resulting in muscular discomfort & pain. In a pilot‐proof of concept study, we determined the effects of MSM on markers of exercise recovery & performance.MethodsIn random order 24 moderately exercise‐trained men (25.5±5.6 yrs) received MSM 3.0 gm/d or PLA, for 14 days, with a 17‐day washout between. The study included 3 tests: baseline, no product & the 2nd & 3rd following 14d supplementation with MSM & PLA. Each test consisted of 2 visits. At the 1st visit, subjects performed stressing exercise; 28 total sets of leg extensions, sets 1–25, predetermined weight, 10 reps each, sets 26–28 to muscular failure at 70% 1‐RM (performance). At the 2nd visit (48 hrs later), subjects performed 12 total sets of leg ext, sets 1–9, predetermined weight, sets 10–12 to muscular failure, 70% 1‐RM (performance). Muscle discomfort/pain (10‐point VAS scale), inflammation (hs‐CRP & IL‐6), blood antioxidant status (TEAC & SOD), & homocysteine were measured before the stressing exercise and 2 & 48 hours post exercise. Exercise performance was also measured following 14d supplementation with MSM/PLA (sets 26–28 and sets 10–12). In order to eliminate sequence effects, results are provided on the 1st product as compared to baseline (comparison of the 1st & 2nd tests).ResultsMSM intervention resulted in significantly less pain/discomfort vs. PLA from baseline to 2 hrs (1.55±0.82 vs 3.75±2.58, p=0.012). Change in IL‐6 was significant within the MSM & PLA & between MSM (0.54±0.76) vs PLA (−0.58±0.97) p = 0.006. There were no significant differences between MSM & PLA noted for the other biomarkers.ConclusionMSM may help alleviate the discomfort/pain that can follow a stressful exercise session.

Leptin knockdown reduces innate immune function in zebrafish

We investigated innate immune function in developing zebrafish with reduced leptin expression (via antisense morpholino technology). Leptin is a pleiotropic, adipose derived hormone known to be involved in mammalian lipid mobilization and storage, as well as the maintenance of many peripheral systems such as immune function. Despite many well‐described effects in mammals, leptin's function(s) in lower vertebrates are still poorly resolved. A fluorescent strain of P. aeruginosa was used to challenge the immune system of developing zebrafish and to visualize the progression of infection. Leptin knockdown significantly reduced the ability to fight invading pathogens, which was reflected in both reduced survivability and increased bacterial load of leptin morphants. Overall, these data suggest that leptin signaling influences innate immune function in fishes as it does in mammals, and promotes zebrafish as another vertebrate model for studying leptin function.

The Synthetic Progestin Levonorgestrel Is a Potent Androgen in the Three-Spined Stickleback (Gasterosteus aculeatus)

The use of progestins has resulted in contamination of aquatic environments and some progestins have in experimental studies been shown to impair reproduction in fish and amphibians at low ng L(-1) concentrations. The mechanisms underlying their reproductive toxicity are largely unknown. Some progestins, such as levonorgestrel (LNG), exert androgenic effects in mammals by activating the androgen receptor (AR). Male three-spined stickleback (Gasterosteus aculeatus) kidneys produce spiggin, a gluelike glycoprotein used in nest building, and its production is directly governed by androgens. Spiggin is normally absent in females but its production in female kidneys can be induced by AR agonists. Spiggin serves as the best known biomarker for androgens in fish. We exposed adult female sticklebacks to LNG at 5.5, 40, and 358 ng L(-1) for 21 days. Androgenic effects were found at LNG concentrations ≥40 ng L(-1) including induction of spiggin transcription, kidney hypertrophy, and suppressed liver vitellogenin transcription. These are the first in vivo quantitative data showing that LNG is a potent androgen in fish supporting the contention that androgenic effects of certain progestins contribute to their reproductive toxicity.