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The chemistry of brevetoxins: a review.

The structure of the unique 'red tide' dinoflagellate neurotoxin, brevetoxin-B is presented and the experimental data supporting the chemical structure is discussed. A brief account of the other brevetoxins and their structural relationships is also presented. A biosynthetic scheme for the natural formation of the brevetoxin skeleton is proposed. Studies of the most toxic of the three pure brevetoxins, brevetoxin-A, indicate a skeleton differing from that of brevetoxin-B.

Chemical Phenomena↗

Brevetoxin binding: molecular pharmacology versus immunoassay.

Brevetoxin PbTx-3 isolated from Florida's red tide dinoflagellate Ptychodiscus brevis has been produced recently in tritiated form by reductive tritiation of brevetoxin PbTx-2. Tritiated PbTx-3 has been used as a specific probe in competitive radioimmunoassays developed to detect brevetoxins in food sources, and this probe has also been utilized to characterize the brevetoxin binding component in rat brain synaptosomes. Brevetoxins PbTx-2 and PbTx-3, possessing the same structural backbone (type-1) as the tritiated probe, and PbTx-1 and PbTx-7, possessing a second structural backbone (type-2), have been compared quantitatively in their individual abilities to competitively displace tritiated PbTx-3 from its specific binding site in each assay. Type-1 toxins displaced labeled probe with ED50 values of 20-22 nM and 12-17 nM in radioimmunoassay and synaptosomes, respectively. Type-2 toxins displaced labeled probe with ED50 values of 92-93 nM and 3.5-4.1 nM in RIA and synaptosomes, respectively. Synaptosome assays reflect potency of each toxin examined, while radioimmunoassay reflects structural similarities to the immunizing toxin PbTx-3.

Animals↗

Respiratory effects of brevetoxin and saxitoxin in awake guinea pigs.

Ptychodiscus brevis toxin (brevetoxin) is associated with 'Florida red tide' and cause neurotoxic shellfish poisoning. Saxitoxin is the agent of paralytic shellfish poisoning. Clinical reports of human intoxication suggest that both toxins affect the respiratory system. The toxins were administered by slow intravenous infusion. The effects of the toxins on respiratory function of awake guinea pigs in a pressure plethysmograph were studied. Both toxins caused lactic acidosis of unknown etiology, which was compensated for by increased minute volume with brevetoxin (PbTx-3)- but not with saxitoxin-intoxicated animals. In general, brevetoxin increased ventilation, before respiratory failure, while saxitoxin had a depressive effect on ventilation. Airways resistance was not increased, nor was dynamic compliance decreased during intoxication, although the data suggest that respiratory system failure was the primary cause of death. The responses seen in these experiments are consistent with the dissimilar molecular actions of these toxins.

Animals↗

Presence of saxitoxin in toxic extracts from Gonyaulax polyedra.

A "red tide" bloom of Gonyaulax polyedra occurred in Italy in Autumn, 1988. Algal concentrated extracts and undiluted water samples from the bloom were tested both with the Microtox system and a mouse bioassay, revealing the presence of paralytic shellfish poison-like neurotoxins. Saxitoxin levels evaluated on the basis of toxicological and instrumental analysis showed discrepancies. Other toxins could be present in addition to paralytic shellfish poison.

Animals↗

Effect of lyophilization on the stability of gonyautoxins obtained from contaminated mussels.

This study describes the stability of gonyautoxins (GTX) and C toxins obtained from contaminated mussels and stored at different temperatures in lyophilized samples. Analyses of extracts from mussels contaminated with paralytic shellfish poison (PSP) indicated the presence of gonyautoxins as the major component in red tides of the North-West coast of Spain. These GTX and C toxins were extracted from contaminated mussels (Mytilus galloprovincialis Lmk) and partially purified by chromatography on Bio-Gel P-2 and Bio-Rex 70. The stability of these toxins was analysed by high performance liquid chromatography. GTX 4 and GTX 6 are the most stable toxins among GTX. We conclude that the lyophilization procedure is not the safest way to process most of the gonyautoxins. However, the lyophilization procedure made the C toxins unstable, so clearly this procedure must be rejected.

Animals↗

The site of action of Ptychodiscus brevis toxin within the parasympathetic axonal sodium channel h gate in airway smooth muscle.

The red tide toxin produced by Ptychodiscus brevis ( PBTX ) may cause cough, sneezing, and asthma. Previous in vitro studies with isolated canine tracheal smooth muscle demonstrated that PBTX stimulates sodium channels of parasympathetic nerve endings and thus causes a contractile response. The present study investigated the mechanism of the PBTX effect on canine tracheal smooth muscle. Repeated exposure of the muscle strip to PBTX (final concentration 46 micrograms/ml) followed by washout of the toxin resulted in reestablishment of baseline tension but a failure of contraction on further addition of PBTX . However, veratridine and scorpion toxin (SCT), which are voltage-sensitive sodium channel activators, still induced contraction. Furthermore, the contraction caused by veratridine was enhanced by a high dose of PBTX , whereas contraction caused by SCT was not. Responses to veratridine and SCT as well as PBTX (previously reported) were blocked by tetrodotoxin (a sodium channel blocker), while acetylcholine responsiveness remained intact. These results indicate that PBTX receptors in parasympathetic nerves influence Na+ flux at the h gate, that these receptors differ from the veratridine and SCT receptors, and that the conformational change in the receptors induced by PBTX affects the tissue response to veratridine.

Animals↗

The mechanism of Ptychodiscus brevis toxin-induced rat vas deferens contraction.

Ptychodiscus brevis, which causes Florida red tide, produces Ptychodiscus brevis toxin (PBTX) known to contain neurotoxins and to induce rhinorrhea, tearing, and cough in normal humans and wheezing in asthmatic subjects. It was previously reported (J Allergy Clin Immunol 69:418, 1982; 73:824, 1984) that PBTX causes canine tracheal smooth muscle contraction via stimulation of sodium channels in the axons of parasympathetic postganglionic nerves and the release of acetylcholine from these nerve endings. This was postulated to be an asthma-triggering mechanism. In this article the toxins were evaluated to determine if they also stimulate sodium channels on adrenergic nerve endings and release norepinephrine. Rat vas deferens was selected as the experimental tissue. Both PBTX and norepinephrine contracted rat vas deferens. Prazosin 10(-6) mol/L blocked the response to PBTX (3 micrograms/ml) (88.3% to 27.3% contraction [n = 6; p less than 0.001]) and the response to norepinephrine (EC50 was shifted from 1.67 X 10(-6) mol/L to 1.25 X 10(-4) mol/L in the presence of prazosin 10(-6) mol/L [n = 6; p less than 0.001]). Phentolamine 10(-6) mol/L also blocked both PBTX and norepinephrine. Tetrodotoxin 10(-7) mol/L, a sodium channel blocker, completely blocked the response to PBTX but not to norepinephrine. The response to PBTX was significantly reduced from 1.53 gm of tension in controls to 0.29 gm of tension (n = 6; p = 0.002) in tissues obtained from rats pretreated with reserpine (2 mg/kg per day for 2 days, injected intraperitoneally). Verapamil 10(-5) mol/L blocked the PBTX response, and PBTX caused no contraction in calcium-free media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Seasonal changes in an intertidal community affected by sewage pollution.

Seasonal changes in structure of a rocky intertidal community affected by sewage pollution at Quequén (Argentina) were studied over a period of 2 years. Most species showed a decrease in cover values in the polluted area. On the other hand, a small proportion of organisms favoured by organic enrichment predominated around the outfall during the period of study. Community structure was not significantly altered by frosts or windstorms. Desiccation is identified as the main physical stress. A combination of late spring high temperatures with extreme midday low-tides caused by northerly winds was responsible for heavy losses in dominant algae. Major seasonal changes in community structure were primarily due to variations in area covered by the chlorophyte Ulva lactuca, and crusts of blue-green algae and diatoms in the vicinity of the outfall. Highest diversity values were attained during either late winter or spring, due to increased abundances of several seasonal algae. Abundance of the dominant organism, the bivalve Brachidontes rodriguezi, remained stable, showing only slight, non-seasonal, changes. Since the absence of B. rodriguezi is an indication of heavy pollution, temporal stability of this species suggests that the intensity of sewage discharges did not vary over the period of study.

Journal Article↗

Three decades of tributyltin in the coastal environment with emphasis on Arcachon Bay, France.

This account briefly reviews the fate, bioconcentration and effects of tributyltin (TBT) three decades after its introduction into the coastal environment. Data on TBT-related events that occurred in Arcachon Bay (gastropod imposex, oyster recruitment failure, oyster shell malformations, concentrations in water and sediments) are revised and reinterpreted. Historically, TBT concentrations in the waters of the open bay seldom exceeded 1 ng Sn l(-1) in the 1960s, likely surpassed the range of 100 ng Sn l(-1) from 1977 to 1981 (years when no oyster spat were collected and the local shellfish industry collapsed), and decreased to about 1 ng Sn l(-1) in the late 1980s and early 1990s following legislation in January 1982 banning TBT use. TBT pollution is discussed in relation to the green tides that have developed in Arcachon Bay since 1982.

Journal Article↗

Scientific information in judicial and administrative systems.

There has arisen in recent times an increasing concern for the quality and interpretation of scientific and technical facts in both administrative (regulatory) and judicial decisions dealing with environment and health. Members of the scientific community have pointed to the poor quality of the scientific fabric used as the factual basis for decisions. Others fear an erosion of justice (as in the awarding of just compensation) if an excessively rigorous test for judging scientific material is demanded. Perhaps most important, this complex issue has made more explicit a debate over where the boundaries properly lie between scientific and social issues and how broadly those decisions should be shared. The emergence of this issue of how science should articulate with the public policy process follows a number of important trends of the past few years. One is a much augmented degree of public interest in health and risks to health. The rising tide of public concern for the environment of the past two decades turned in great part around issues of health--often as a surrogate for other environmental qualities. This coincided with a period of increasing public demand for more direct public participation in the affairs of government. All of this together brought forth much more scientific and technical detail into broader public discussion than had been the pattern historically. Thirdly, the nation has turned to its courts more frequently and more prominently both to render ultimate decisions for the regulatory process and to review cases brought in the name of compensation for disease and disability. As a result of this latter, increasingly complex scientific and technical evidence has become the centerpiece of adversary proceedings and the court has become the locus for judging and interpreting science. In some cases, science itself has become the principal fodder for argumentation--leading to a debate over a seeming conflict between honoring the integrity of the factual basis for decisions versus the serving of a variety of social goals. In fact, both of these should be well accommodated. Decisions should rest on a respected body of fact and ultimate decisions should serve desired social endpoints. However, that dictates a separation between review and interpretation of scientific factual material from adversary proceedings. This has been the traditional experience in other parts of the western world. To perform in this way, however, does raise fundamental questions about how political power for these decisions should be shared.

Disability Evaluation↗

Paradise lost: an introduction to the geography of water pollution in Puerto Rico.

Rapid industrialization has transformed the agricultural economy of Puerto Rico, creating employment opportunities and raising standards of living. Success, however, is marred by widespread pollution that outstrips the infrastructural capacity necessary for the preservation of environmental quality and of human health. The result today is a landfill crisis, a heritage of toxic dumps, and an advancing tide of pollution. Rivers and reservoirs are nearly ubiquitously affected and groundwaters, long thought to be naturally protected, show evidence of increasing contamination. Limestone aquifers are at particular risk. Public awareness and inter-sectoral political leadership are urgently needed to reverse the trend towards environmental deterioration.

Developing Countries↗

Diagnostic, therapeutic, didactic, data bank utilization of computerized monitoring in a critical care center.

At the beginning of their discovery informatic technique procedures and methodologies generated a great wave of hopes for progress in theoretical and practical fields of human activity, but when passing to concrete application, an ebb phase followed. Recent theoretical and technical progress, however, has generated an enormous new up-surge of interest for applications of informatic processing in all fields of science. Medicine in the last three decades has gone through the same phases observed in other disciplines. In the ICU the potentiality of exploitation of the informatic techniques appeared enormous, however, initially from a practical point of view it found only limited, sectorial experimentation and implementation, but afterwards a limited and slow process of parcellar infiltration, the high tide of informatic, has broken the dam and deeply advanced in its territory, obliging the staff to a great effort of cultural and technical updating to cope with it. After recalling some of the history of Computer Science or Informatic, even if history was only yesterday, we will present some examples of the hand made experience of an ICU, (namely ours) with limited economical resources, and whose interest in this field arises from actual needs, personal interest and enthusiasm of a staff who works, on its free time, after fulfilling its stressing routine.

Computers↗

13C-NMR study of the binding of [1-13C]galactose-labelled N-acetyllactosamine and [1-13C]galactose-enriched hen ovalbumin to soybean agglutinin.

The binding of the tide compounds to soybean agglutinin was investigated using 13C-NMR spectroscopy. The equilibrium constant for the binding of N-acetyllactosamine was found to be smaller than that obtained for the binding of ovalbumin (1.1 X 10(3) vs. 7.4 X 10(3) M-1). Only two binding sites per lectin tetramer were determined for the binding of ovalbumin, which is half the number of binding sites reported for the binding of small ligands to the lectin. Steric interference between the bulky ovalbumin molecules is believed to be the reason for the observed decrease in the apparent number of binding sites on the lectin.

Amino Sugars↗

Occurrence and possible adaptive significance of some histochemically demonstrable dehydrogenases in two entosymbiotic rhabdocoels (Platyhelminthes: Turbellaria).

1. The occurrence and distribution of twelve dehydrogenases have been studied histochemically in two species of rhabdocoel turbellarians entosymbiotic in marine bivalves. 2. Both species (Paravortex scrobiculariae in Scrobicularia plana and P. cardii in Cerastoderma edule) possess dehydrogenases concerned with the three major energy-producing pathways. 3. P. scrobiculariae shows a much greater emphasis on glycolysis than does P. cardii. 4. It is suggested that the emphasis on glycolysis in P. scrobiculariae is an adaptation to regular variations in oxygen supply in its habitat; this adaptation facilitates feeding and associated migrations within the host which occur at times when the host is not submerged by the tide and when oxygen is likely to be in short supply. 5. Dehydrogenases associated with the pentose phosphate shunt are especially evident in the developing embryos of both species and are probably concerned with synthesis of nucleotides and nucleoproteins.

Alcohol Dehydrogenase↗

Effect of human insulin administration on urinary acidification in patients with insulin-dependent diabetes.

A previous study has shown that oral glucose administration results in a transient fall in urinary acid excretion in humans. The present study was undertaken to determine the effect of physiologic doses of insulin on urinary acidification while maintaining serum glucose concentration constant. This was accomplished by using a euglycemic insulin clamp method. Eight patients with insulin-dependent diabetes and no clinical or laboratory evidence of detectable renal disease were studied. Data obtained during two 2-hour periods of steady state insulin infusion rates of 0.2 and 0.5 mU/kg/min were compared. This resulted in steady state serum free insulin levels of 15 +/- 0.1 and 39 +/- 0.6 uU/ml respectively. Urinary pH and bicarbonate excretion rate rose while the excretion rates of titratable acid, ammonium and net acid fell significantly with increased insulin administration. These changes occurred in the absence of any significant changes in serum glucose, potassium, Ca2+ or phosphorus concentrations or urinary excretion rates of Na+, K+, phosphorus or Ca2+. These data suggest that increased insulin levels within the physiological range can result in a transient fall in the rate of urinary acid excretion. These findings confirm previous observations in animals and suggest that insulin may be the cause of post prandial urinary "alkaline tide".

Adult↗

Whale strandings: hypothesis.

The hypothesis is presented that whales become stranded inadvertently as a consequence of seeking stimulation. The animals enter shallow water in order to roll over, bask, and rub themselves in the sand, and are trapped by the receding tide. It suggested that stimulation-seeking behavior (and stranding) reflects a general sympathetic nervous system response which may be due to a number of factors such as pain, discomfort, reproductive state, and other biorhythmic changes.

Animals↗

Brevetoxin depresses synaptic transmission in guinea pig hippocampal slices.

Extracellular recordings were obtained from area CA1 of guinea pig hippocampal slices. PbTx-3, a brevetoxin fraction isolated from the red tide dinoflagellate Ptychodiscus brevis, was applied by bath perfusion. The toxin produced a concentration-dependent depression of the orthodromically evoked population spike with an EC50 of 37.5 nM. Brevetoxin concentrations below 10 nM were without effect, and concentrations above 100 nM led to total inhibition of evoked responses. PbTx-3 did not produce spontaneous synchronous discharges but did induce afterdischarges following evoked responses in about 50% of the slices tested, particularly at concentrations between 10 nM and 100 nM. Orthodromically evoked responses were more sensitive to PbTx-3 than were those elicited by antidromic stimulation. High-Ca2+ solution, 4-aminopyridine, and tetraethylammonium failed to antagonize either orthodromic or antidromic effects of the toxin. Although the precise mechanism by which PbTx-3 depresses evoked responses is not certain, depolarization of the presynaptic nerve terminals leading to failure of transmitter release could explain the toxin's actions. This is the first report of the effects of brevetoxin applied directly to central nervous system tissue.

Animals↗

Ethnomedical and ethnobotanical investigations among some scheduled caste communities of Travancore, Kerala, India.

Investigations were conducted on the traditional life, culture and medical lore of some prominent scheduled caste communities, namely Pulayar, Kuravar, Vedar, Parayar and Nayadi, inhabiting the Travancore region of Kerala. These communities were perhaps some of the original inhabitants of Kerala who have evolved their own peculiar cultural traditions, religious customs, cults, totems, legends, myths, folklores and medicinal practices. But in recent years these communities are being enveloped in the rising tide of civilization and their age old cultural heritage and knowledge systems are fast disappearing. Considering the great importance of conserving/preserving this knowledge system the present study was undertaken. Much interesting information on the cultural life of these communities was gathered. Special attention was paid to the study of their medicinal practices which is essentially a magico-religious-herbal therapy. These tribals have an indepth knowledge of the surrounding flora and utilize over 500 plant species for treating various ailments. The present communication reports only those medical claims for plants that have not been previously published.

Ethnicity↗