Environmental toxicants and effects on female reproductive function.

One of the most toxic substances known to humans, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), is also highly pervasive in the environment. It is created naturally in volcanic eruptions and forest fires, and anthropogenically in waste incineration, chlorination processes and certain plastics manufacture. From reports of large industrial and other accidents, or from experimental studies, dioxin exposure has been correlated in animal models and/or humans with chloracne of the skin, organ cancers, hepatotoxicity, gonadal and immune changes, pulmonary and other diseases such as diabetes, skewing of the sex ratio, and infertility.

The physiology and evolution of urea transport in fishes.

This review summarizes what is currently known about urea transporters in fishes in the context of their physiology and evolution within the vertebrates. The existence of urea transporters has been investigated in red blood cells and hepatocytes of fish as well as in renal and branchial cells. Little is known about urea transport in red blood cells and hepatocytes, in fact, urea transporters are not believed to be present in the erythrocytes of elasmobranchs nor in teleost fish.

Use of urea as a chemosensory cloaking molecule by a bony fish.

Because urea is bioenergetically expensive to synthesize, few aquatic teleostean (bony) fish make or excrete much urea beyond early development and excrete the majority of nitrogenous waste as the readily diffusible ammonia. The gulf toadfish is one of a few adult teleostean fish that excretes predominantly urea. Most studies of chemosensing by fish predators have focused on amino acids as odorants, but we tested the chemo-attractiveness of both urea and ammonia.

Piscine insights into comparisons of anoxia tolerance, ammonia toxicity, stroke and hepatic encephalopathy.

Although the number of fish species that have been studied for both hypoxia/anoxia tolerance and ammonia tolerance are few, there appears to be a correlation between the ability to survive these two insults. After establishing this correlation with examples from the literature, and after examining the role Peter Lutz played in catalyzing this convergent interest in two variables, this article explores potential mechanisms underpinning this correlation. We draw especially on the larger body of information for two human diseases with the same effected organ (brain), namely stroke and hepatic encephalopathy.

Copper toxicity across salinities from freshwater to seawater in the euryhaline fish Fundulus heteroclitus: is copper an ionoregulatory toxicant in high salinities?

Two waterborne Cu exposures were performed to investigate if Cu is an ionoregulatory toxicant at all salinities in the killifish, Fundulus heteroclitus. A 30-day flow through exposure in 0 (FW), 5, 11, 22, and 28 ppt (SW) and three [Cu]'s (nominal 0, 30, and 150 microg Cu L(-1)) revealed no apparent Cu induced mortality at the intermediate salinities and high mortality in FW and SW. Fish were sampled at 4, 12, and 30 days after the start of the exposure and both Na+/K+ adenosine triphosphatase (Na+/K+ ATPase) and carbonic anhydrase (CA) activity in the gill and intestine as well as whole body [Na+], and [Cl-] were measured.

Effects of salinity on copper accumulation in the common killifish (Fundulus heteroclitus).

Results of laboratory and field studies have demonstrated that salinity influences the accumulation of copper. The present study is, to our knowledge, the first to examine the effect of salinity on copper accumulation in a teleost fish across a comprehensive range of salinity from freshwater to seawater. This was done in an effort to identify potential target tissues and differences in chemical interactions across salinities that will aid in the development of a seawater biotic ligand model (BLM) for copper.

Ammonia affects brain nitrogen metabolism but not hydration status in the Gulf toadfish (Opsanus beta).

Laboratory rodents made hyperammonemic by infusing ammonia into the blood show symptoms of brain cell swelling and increased intracranial pressure. These symptoms could be caused in part by an increase in brain glutamine formed when brain glutamine synthetase (GS) naturally detoxifies ammonia to glutamine. Previous studies on the Gulf toadfish (Opsanus beta) demonstrated that it is resistant to high ammonia exposure (HAE) (96 h LC(50)=10mM) despite an increase in brain glutamine.

Neurobehavioral effects of harmful algal bloom (HAB) toxins: a critical review.

Human exposure to naturally occurring marine toxins has been associated with a range of neurobehavioral abnormalities. The toxins are produced by harmful algal blooms (HABs) and are typically contracted through seafood consumption. The primary target of many of the HAB toxins is the neurologic system, and the neurobehavioral symptoms associated with the HAB illnesses have influenced public health policy.

An Epidemiologic Approach to the Study of Aerosolized Florida Red Tides.

Very little has been published in the scientific literature on the human health effects of Florida red tide, either as human clinical case reports or formal epidemiologic studies. In addition to the health effects associated with the ingestion of contaminated shellfish, there have been multiple anecdotal reports of respiratory irritation and possible immunologic effects associated with the inhalation of aerosolized Florida red tide. To investigate the human health effects from environmental exposure to red tide toxins, we have formed an interdisciplinary team of scientists.

Metabolic fate of exogenous 15NH4Cl in the gulf toadfish (Opsanus beta).

This study was undertaken to determine whether gulf toadfish (Opsanus beta) could metabolize ammonia from their environment into other, less toxic products. To this end, gulf toadfish were exposed to 3.8 mM 15NH(4)Cl in seawater for 24 and 48 h.

Toxicogenomic effects of marine brevetoxins in liver and brain of mouse.

Although the polyether brevetoxins (PbTx's) produced by Karenia brevis (the organism responsible for blooms of the Florida red tide) are known to exert their acute toxic effects through ion-channel mediated pathways in neural tissue, prior studies have also demonstrated that at least one form of the toxin (PbTx-6) is bound avidly by the aryl hydrocarbon receptor (AhR). Since AhR binding of a prototypical ligand such as dioxin is the first step in a cascade pathway producing major changes in gene expression, we reasoned that PbTx-6 might produce similar genomic-wide changes in expression. Mice were injected i.

A second glutamine synthetase gene with expression in the gills of the gulf toadfish (Opsanus beta).

We characterized the expression of the nitrogen metabolism enzyme glutamine synthetase [GSase; L-glutamate: ammonia ligase (ADP-forming), E.C. 6.

Activation of the rainbow trout metallothionein-A promoter by silver and zinc.

In fish, the synthesis of metallothionein (MT) is increased by a number of heavy metals. The rainbow trout MT-A gene promoter region contains six known metal responsive elements (MREs), that mediate promoter activation by metals. In the present study, two fish cell lines differing in their ability to produce MT, RTG-2 (produce MT protein) and CHSE-214 (produce no detectable MT protein), were used to help elucidate the roles of Zn, Ag and MT in the activation of the MT promoter.

Transgenic zebrafish model of neurodegeneration.

In Alzheimer's disease (AD), the microtubule-associated protein, tau, is compromised in its normal association with microtubules and forms into paired helical filaments (PHF) that are the hallmark cytoskeletal pathology of the disease. Several posttranslational modifications of tau including phosphorylation have been implicated in AD pathogenesis. In addition, and importantly, mutations in the genes encoding human tau have recently been implicated in a variety of hereditary dementias, collectively termed frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17).

Chemosensors for the marine toxin saxitoxin.

Eleven anthracylmethyl crown ethers have been synthesized and evaluated as fluorescence sensors for the marine toxin saxitoxin. Fluorescence enhancement data are consistent with a 1:1 binding complex for all crowns. The binding constants are in the range of 10(4) M(-)(1) in ammonium phosphate buffer (pH 7.

Estrous cycle-regulated expression of CYP1B1 mRNA in the rat ovary.

CYP1B1, a member of the cytochrome p450 superfamily, is expressed constitutively in the steroidogenic tissues of mammals and is inducible by peptide hormones, cAMP and aromatic hydrocarbon receptor (AHR) ligands. The mechanism of induction of this cytochrome p450 is similar to that for CYP1A1, i.e.

Trimethylamine oxide accumulation in marine animals: relationship to acylglycerol storage.

Trimethylamine oxide (TMAO) is a common and compatible osmolyte in muscle tissues of marine organisms that is often credited with counteracting protein-destabilizing forces. However, the origin and synthetic pathways of TMAO are actively debated. Here, we examine the distribution of TMAO in marine animals and report a correlation between TMAO and acylglycerol storage.

An improved synthesis of a trifurcated newkome-type monomer and orthogonally protected two-generation dendrons.

The one-step synthesis of amino-polyether tri-tert-butyl ester monomer 2, by condensation of TRIS with tert-butyl acrylate, is reported. The nitrogen of the monomer can be protected with a Cbz group; subsequent removal of the tert-butyl esters with formic acid affords a triacid that is coupled to three monomers to afford an orthogonally protected two-generation, trifurcated polyether-polyamide dendron. The Cbz protecting group may be removed from the second-generation dendron without disturbing the tert-butyl esters of the periphery.

Lack of effect of beta-naphthoflavone on induction of Nramp genes in adult rainbow trout Oncorhynchus mykiss.

Natural resistance-associated macrophage protein (Nramp) genes in rainbow trout, Oncorhynchus mykiss, were identified and characterized. The greatest mRNA level encoding these genes was in the developing ovary of rainbow trout. We evaluated the response of these genes to a certain aromatic hydrocarbon receptor (AHR) agonist.

Oxidative stress in zebrafish cells: potential utility of transgenic zebrafish as a deployable sentinel for site hazard ranking.

In order to quickly assess potential environmental hazards of forwardly deployed military bases, we have focussed our efforts on biochemical and molecular changes in vertebrate cells following exposure to aqueous soil extracts. To this end, we are designing a series of deployable transgenic fish. Fish exhibit many of the same general defenses against toxic chemicals as do mammals, including enzyme induction, and the generation of oxidative stress.

Do circulating plasma AVT and/or cortisol levels control pulsatile urea excretion in the gulf toadfish (Opsanus beta)?

Previous work has shown that pulsatile urea excretion at the gills of the gulf toadfish is due to periodic activation of a facilitated diffusion transport system with molecular and pharmacological similarity to the UT-A transport system of the mammalian kidney. In mammals, AVP and glucocorticoids are two important endocrine regulators of this system. The present study focused on the potential role of circulating AVT (the teleost homologue of AVP) and cortisol levels as possible triggers for urea pulses.

Physiological and molecular characterization of urea transport by the gills of the Lake Magadi tilapia (Alcolapia grahami).

The Lake Magadi tilapia (Alcolapia grahami) is an unusual fish, excreting all its nitrogenous waste as urea because of its highly alkaline and buffered aquatic habitat. Here, using both physiological and molecular studies, we describe the mechanism of branchial urea excretion in this species. In vivo, repeated short-interval sampling revealed that urea excretion is continuous.

High ammonia tolerance in fishes of the family Batrachoididae (Toadfish and Midshipmen).

Three fish species of the family Batrachoididae, the gulf toadfish (Opsanus beta), the oyster toadfish (Opsanus tau), and the plainfin midshipman (Porichthys notatus) demonstrated exceptionally high tolerances to elevated water ammonia with 96-h LC50 values of 9.75, 19.72 and 6 mM total ammonia, respectively.

Molecular characterization of a urea transporter in the gill of the gulf toadfish (Opsanus beta).

Urea excretion by the gulf toadfish (Opsanus beta) has been shown in previous studies to be a highly pulsatile facilitated transport, with excretion probably occurring at the gill. The present study reports the isolation of an 1800 base pair (kb) cDNA from toadfish gill with one open reading frame putatively encoding a 475-residue protein, the toadfish urea transporter (tUT). tUT, the first teleostean urea transporter cloned, has high homology with UTs (facilitated urea transporters) cloned from mammals, an amphibian and a shark, and most closely resembles the UT-A subfamily.

Brevetoxin modulates neuronal sodium channels in two cell lines derived from rat brain.

Single Na+ channel currents were recorded from cell-attached membrane patches from two neuronal cell lines derived from rat brain, B50 and B104, and compared before and after exposure of the cells to purified brevetoxin, PbTx-3. B50 and B104 Na+ channels usually exhibited fast activation and inactivation as is typical of TTX-sensitive Na+ channels. PbTx-3 modified channel gating in both cell lines.