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PubMedDate not supplied

Magnesium and cardiovascular drugs: interactions and therapeutic role.

Numerous experimental, epidemiological and clinical studies have pointed out a relevant role for magnesium deficiency in the development of many cardiovascular diseases. Some pharmacological treatments may interfere with magnesium turnover, and magnesium deficiency may alter the pharmacokinetics and pharmacodynamics of some cardiovascular drugs. Loop and thiazide-like diuretics increase magnesiuresis, and total bodily magnesium deficiency may appear during prolonged treatment with diuretically active doses of these drugs. The potassium retaining agents, such as amiloride, triamterene and spironolactone, tend to retain magnesium but they are not magnesium-retaining substances to the extent to which they are potassium-retaining diuretics. The interaction between magnesium and digitalis is complex. Magnesium, acting as an indirect antagonist of digoxin at the sarcolemma Na(+)-K(+)-ATPase pump, reduces cardiac arrhythmias due to digoxin poisoning. Recent controlled studies have shown that treatment with magnesium significantly reduces the frequency and complexity of ventricular arrhythmias in digoxin-treated patients with congestive heart failure without digoxin toxicity. Magnesium improves the efficacy of digoxin in slowing the ventricular response in atrial fibrillation. Digoxin reduces tubular magnesium reabsorption, and in patients with congestive heart failure this interaction may be cumulative with other causes of magnesium deficiency (diuretics, diet, poor intestinal absorption). The complex and potentially life-threatening interactions between magnesium and some cardiovascular drugs suggest that magnesium status should be carefully monitored in patients receiving such drugs. Therapy with magnesium is rapidly acting, has a safe toxic-therapeutic ratio, is easy to administer and titrate. The correction of magnesium deficit should therefore always be considered for patients with cardiopathy.

Cardiovascular Agents↗
PubMed2003

Absence of tumor promoting activity of Euphorbia milii latex on the mouse back skin.

Euphorbia milii (Euphorbiaceae) is a decorative plant used in gardens and living fences. In China, it has also been employed in herbal remedies for hepatitis and abdominal edema. Since E. milii latex--lyophilized or in natura--proved to be a potent plant molluscicide, its toxicity to non-target organisms has been comprehensively studied. Concerns on a possible tumor promoting activity have discouraged its use as a locally-available alternative molluscicide in schistosomiasis control programs. Two in vitro assays (inhibition of metabolic cooperation in V79 cells and Epstein-Barr virus induction in Raji cells) had suggested that E. milii latex contained tumor-promoting substances. This study was undertaken to verify whether the latex acts as a tumor promoter in vivo as well. A single dose of the initiating agent DMBA (400 nmol) was applied on the back skin of male and female DBA/2 mice. Testing for tumor promoting activity began 10 days after initiation. Tetradecanoyl phorbol acetate (TPA) (5 nmol, positive control), lyophilized latex (20, 60 and 200 microg per mouse) or acetone (vehicle control) were applied on mouse back skin twice a week for 20 weeks. In TPA-treated mice, papillomas were firstly noted during the 11th week, and by the 17th week all animals exhibited skin tumors. No tumors developed in mice treated with the solvent alone and in those exposed to latex. Findings from the present study therefore indicated that E. milii crude latex does not act as a tumor promoting agent on the mouse back skin assay.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Risk assessment for children and other sensitive populations.

Children form a unique subgroup within the population who require special consideration in risk assessment. Children are not little adults. Their tissues and organs grow rapidly, developing and differentiating. These development processes create windows of great vulnerability to environmental toxicants. Furthermore, the exposure patterns of children to environmental chemicals are very different from those of adults. Traditional risk assessment has generally failed to consider the special exposures and the unique susceptibilities of infants and children. Adoption of a new child-centered agenda for research and risk assessment is necessary if disease in children of toxic environmental origin is to be identified, understood, controlled, and prevented. This agenda needs to be multidisciplinary. Specific requirements within the agenda include: (1) exploration and quantification of unique patterns of exposure for children; (2) adoption of new, more sensitive approaches to testing chemicals that can recognize the consequences of exposure during early development; (3) identification, through clinical and epidemiologic studies, of etiologic associations between environmental exposures and pediatric diseases; and (4) elucidation, at the cellular and molecular levels, of the pathogenetic mechanisms of pediatric environmental illness. In the United States, an important start toward adoption of this new agenda has occurred since passage of the Food Quality Protection Act in 1996. A Presidential Executive Order on Children's Health and the Environment has been promulgated. This Order requires all federal agencies to make protecting the health of children against environmental hazards a high priority. A new Office of Children's Health Protection has been established at the U.S. Environmental Protection Agency. Programs in children's environmental health have been created at the Centers for Disease Control and Prevention, the Agency for Toxic Substances and Disease Registry, and the National Institute of Environmental Health Sciences. A national network of eight new Children's Environmental Health Research and Disease Prevention Centers has been formed. These developments will enhance research on previously understudied issues in the environmental health of children and will provide a scientific basis for child-centered risk assessment.

Child↗
PubMed2002

Approaching the problem of bioequivalence of herbal medicinal products.

Herbal medicinal products (HMP) contain exclusively herbal drugs or herbal drug preparations (HDP) and are a complex mixture of different compounds, which may act in an agonistic, synergistic, complementary, antagonistic or toxic way. A specific scientific challenge is for methods to prone the bioequivalence of herbal drug preparations (HDP). Depending on the type of herbal drug preparations, different approaches are possible. If the constituents responsible for therapeutic activity are known, the concept of essential similarity used with chemically defined substances can be fully applied. For extracts with unknown active markers, data on defined chemical constituents are useful for control purposes (charge conformity), but not sufficient to prove bioequivalence. In this case bioassays or pharmacological studies, which measure therapeutically relevant activity, should be used. A phytogeneric is only comparable to the innovator preparation under the following conditions: (i) pharmaceutical equivalence (standardization), (ii) biopharmaceutical equivalence (in vitro dissolution), (iii) bioequivalence with different endpoints (in vitro model, animal model) or (iv) clinical study. An uncritical substitution of herbal drug preparations without considering these scientific criteria should be avoided.

Chemistry, Pharmaceutical↗
PubMed1998

Household insecticides: evaluation and assessment of inhalation toxicity: a workshop summary.

Particularly in tropical countries household insecticides are used on a day-by-day basis to control mosquitoes, other crawling and flying insects to prevent the spread of vector-borne diseases. The products used most often are spray-cans, oil-sprays, mosquito coils as well as slow-release vaporising systems such as mats and liquid vaporiser. The extent and duration of exposure of humans is highly dependent on the type of product used. The objective of this workshop was to analyse the necessity and feasibility of inhalation studies with household insecticides taking into account the specific constrains associated with each type of end-use product. The standardisation of inhalation studies with regard to the generation of test atmospheres, mode and duration of exposure, and selection of adequate toxicological endpoints were addressed. Due to the complex nature of exposure atmospheres generated by some household insecticides, viz. mosquito coils, it is scientifically challenging to characterise the pathomechanism of most concern, since irritant combustion gases, volatile and semi-volatile organic substances, particulates (soot), condensation aerosols and re-condensed substances onto particulates may act independently, synergistically or mixture specific. It has been concluded that for the comparative safety evaluation and risk assessment of indoor insecticide end-use products generally recognised guidance for harmonised inhalation testing is required: 1) For high-dose release products, such as spray-cans, acute inhalation testing appears to be most relevant. 2) For low-dose, slow-release devices, subchronic inhalation studies of 13-weeks, duration of exposure 6 hours/day for 5 consecutive days per week, should be performed on rats preferably with the end-use product. A dose-range finding study of 2-weeks duration, daily exposure, should be available for the justification of dose selection and to demonstrate that the findings of 5 days/week exposure is not different from that utilising a daily exposure. 3) In certain instances, inhalation testing of shorter duration, for example 2 or 4 weeks, may be appropriate if the inhalation toxicity of the basic formula has already been characterised or the major constituents contained in the formulation have been examined in extant studies. The duration of study should also depend on actual use and exposure pattern, the accumulation potential and the mode of action of the ingredients of concern. 4) Particularly for mosquito coil smokes, the possible physico-chemical interactions of particulates, potentially irritant water soluble or nonsoluble vapours and aerosol or vapours of the active ingredient(s) are virtually impossible to predict without appropriate inhalation testing. 5) Physiological measurements may be useful for the detection and quantification of the respiratory tract sensory irritation potency. Biochemical endpoints in lung lavage and conventional histopathology of the lungs and extrathoracic airways are considered to be important. 6) It has been agreed that the nose-only exposure technique provides the most cost-effective and controlled means to expose small laboratory animals to well defined atmospheres as long as the limitations of this technique are taken into account.

Air Pollution, Indoor↗
PubMed1976

Effects of some commercial preparations of polychlorinated biphenyls in growing piglets.

Sixty-four piglets were given ad libitum commercial rations containing 250 ppm of polychlorinated biphenyls as Aroclor 1232, Aroclor 1242 and Aroclor 1254 for periods up to 12 weeks. The toxic effects of the polychlorinated biphenyls upon plasma testosterone levels, the blood coagulation system, the gross- and micropathological changes as well as the extent and differences in their distribution and accumulation were studied. Principals given Aroclor 1232, Aroclor 1242 and Aroclor 1254 for the 12 week period gained 30, 10 and 50% more in body weight respectively than did controls. In the context of the present experiment, Aroclors (especially Aroclor 1254) at 250 ppm level in the ration, appeared to act as growth promoting substances. The mode and site of action of this effect is not known. The gross and micropathological examinations of controls and principals gave no evidence of anomalies. Similarly, the data on various parameters of blood coagulation did not reveal any disturbances. However, testosterone levels in plasma were elevated in male piglets given Aroclors. Analyses of polychlorinated biphenyls showed that the highest concentrations were present in adipose tissues of all treated animals. A cumulative tendency was also evident. The levels were relatively high in brain, in some instances higher than in liver of the same group. Levels in hepatic and muscular tissue were, in many instances, of the same magnitude.

Animals↗
PubMed1998

Opioid toxicity recurrence after an initial response to naloxone.

OBJECTIVE: To determine the frequency and potential predictors of opioid toxicity recurrence after a response to naloxone in adult Emergency Department patients. METHODS: A retrospective case-control study of naloxone-treated patients with opioid toxicity over an 8-year period. Both the patient response to naloxone and recurrence of opioid toxicity was determined by an expert Delphi Panel. The frequency of opioid toxicity recurrence was compared by the duration of opioid effect, the route of opioid exposure, and the presence of other CNS depressant drugs. RESULTS: Ninety of 221 (41%) cases with a discharge diagnosis of opioid toxicity were treated with naloxone; six patients were excluded because of a lack of toxicity. There was a response to naloxone in 50% of the 84 cases, and recurrence of toxicity in 31% (95% CI 17-45%) of naloxone responders. The most common opioids were codeine, heroin, propoxyphene, and oxycodone/hydrocodone. Recurrence of toxicity was more common with long-acting opioids (p = 0.04), and was not associated with the route of opioid exposure (p = 0.42), or presence of ethanol and other CNS depressants (p > or = 0.87). CONCLUSION: Opioid toxicity recurrence after a response to naloxone occurred in approximately 1/3 of adult Emergency Department opioid overdose cases. Recurrence was more common with long-acting opioids and was not associated with the route of opioid exposure. Other clinically useful predictors of toxicity recurrence were not identified.

Administration, Oral↗
PubMed1988

Nephrotoxicity screening in rats: a validation study.

A validation of our non-invasive screening test for the detection of renal damage (Zbinden et al. 1988) is presented. The test is based on repetitive, quantitative urine analysis in groups of six female Sprague-Dawley rats treated on 5 consecutive days with low doses of test substances. Higher doses were administered in the following weeks until nephrotoxic effects or signs of general toxicity were observed. Thirteen reference substances (hexachloro-1:3-butadiene [HCBD], cisplatin, carboplatin, suramin, chloroform, neomycin, rifampicin, phenacetin, phenylbutazone, methicilline, sodium oxalate, ethylene glycol and furosemide) were used. The percentage of rats reaching the test criteria, i.e., pathologic values defined on the basis of measured control values, was determined. In the controls, the overall percentage of rats reaching or exceeding the test criteria was 4.48%, a value that is close to the expected 5%. Evidence of nephrotoxicity was found with all reference compounds. Elevated excretion of cells and occurrence of cylinders were the most sensitive indicators of renal damage. Hematuria was the most frequent finding. Of the other urine constituents measured the enzyme malate dehydrogenase (MDH) was frequently increased. Water consumption, urine volume, pH and specific gravity were occasionally, and protein, glucose, electrolytes, amino acids and gamma-glutamyl-transpeptidase (GGT) were only rarely changed. It is concluded that the screening which is based on quantitative and repeated urine analysis is a useful procedure to detect nephrotoxic chemicals acting by a variety of mechanisms. The histopathological examination of the kidneys contributed useful information of the nature of the toxic effects, but as a screening tool it is less sensitive than quantitative urine analysis.

Animals↗
PubMed2002

Interacting roles of myofibroblasts, apoptosis and fibrogenic growth factors in the pathogenesis of renal tubulo-interstitial fibrosis.

The interrelationship between myofibroblasts and fibrogenic growth factors in the pathogenesis of renal fibrosis is poorly defined. A temporal and spatial analysis of myofibroblasts, their proliferation and death, and presence of transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor-B (PDGF-B) was carried out in an established rodent model in which chronic renal scarring and fibrosis occurs after healed renal papillary necrosis (RPN), similar to that seen with analgesic nephropathy. Treated and control groups (N = 6 and 4, respectively) were compared at 2, 4, 8 and 12 weeks. A positive relationship was found between presence of tubulo-interstitial myofibroblasts and development of fibrosis. Apoptotic myofibroblasts were identified in the interstitium and their incidence peaked 2 weeks after treatment. Levels of interstitial cell apoptosis and fibrosis were negatively correlated over time (r = -0.57, p < 0.01), suggesting that as apoptosis progressively failed to limit myofibroblast numbers, fibrosis increased. In comparison with the diminishing apoptosis in the interstitium, the tubular epithelium had progressively increasing levels of apoptosis over time, indicative of developing atrophy of nephrons. TGF-beta1 protein expression had a close spatial and temporal association with fibrosis and myofibroblasts, whilst PDGF-B appeared to have a closer link with populations of other chronic inflammatory cells such as infiltrating lymphocytes. Peritubular myofibroblasts were often seen near apoptotic cells in the tubular epithelium, suggestive of a paracrine toxic effect of factor/s secreted by the myofibroblasts. In vitro, TGF-beta1 was found to be toxic to renal tubular epithelial cells. These findings suggest an interaction between myofibroblasts, their deletion by apoptosis, and the presence of the fibrogenic growth factor TGF-beta1 in renal fibrosis, whereby apoptotic deletion of myofibroblasts could act as a controlling factor in progression of fibrosis.

Animals↗
PubMed2005

Mutagenicity of Pueraria mirifica Airy Shaw & Suvatabandhu and antimutagenicity of Thunbergia laurifolia Linn.

Thunbergia laurifolia Linn has been reputed to have antitoxic effects for all toxic substances. In this present study, we evaluated its effect against the mutagenicity induced by aqueous extracts from Pueraria mirifica Airy Shaw & Suvatabundhu in male rats. The formation of micronuclei in polychromatic erythrocytes was induced by oral administration of an aqueous extract of P. mirifica at the doses of 400, 600, and 800 mg/kg to the rats for 30 days. The results were that the extracts of P. mirifica at doses of 600 and 800 mg/kg acted as a mutagenic agent by inducing higher frequencies of micronuclei as compared to the controls. For the antimutagenic test, P. mirifica extract at a dose of 600 mg/kg (minimal effective dose) was mixed with fresh and dried extracts of T. laurifolia in proportions of 7:3 and 1:1, respectively. The results of 4-week-treatment indicated that aqueous extracts of T. laurifolia, prepared by both fresh and dry methods, could significantly inhibit the induction of micronuclei as induced by P. mirifica. It could be concluded from the results that, under certain circumstances, T. laurifolia exhibits a significant antimutagenic activity. The use of P. mirifica and T. laurifolia as fusion herbal medicines is suggested.

Acanthaceae↗
PubMed2001

Fatal unintentional occupational poisonings by hydrofluoric acid in the U.S.

BACKGROUND: Case reports have identified hydrofluoric acid (HF) as causing fatal work injury, and HF has both local and systemic toxicity. Surveillance for HF-related mortality is problematic because of the lack of unique coding for this acid in hospital records and vital statistics. METHODS: We identified HF-related fatal work injuries investigated by the Occupational Safety and Health Administration (OSHA) for 1984-94 from coding of Hazardous Substance 1460 (HF) and requested case investigation files under the Freedom of Information Act. We attempted to identify HF-related deaths in the US for the same period through literature case reports, the Consumer Product Safety Commission, and the American Association of Poison Control Centers (AAPCC). RESULTS: For the 11 year period, OSHA investigated nine deaths in eight incidents which involved HF. Four deaths were from skin contact with concentrated HF, and five deaths involved both skin contact and inhalation of vapor. Unsafe work practices were factors in all of the deaths. Calcium chloride or gluconate was noted to have been administered to five of the nine victims. Calcium was administered 90 min after exposure to two victims, and more than 6 h after exposure to a third. We were able to establish that the regional poison control center had been contacted in regard to only one victim. For the period 1984-94, we were able to identify no additional deaths from CPSC reports, one additional death from AAPCC annual reports, and four other deaths from case reports in the medical literature. CONCLUSIONS: For the period of this study, OSHA records identified the greatest number of HF-related fatalities. The limited information in the records suggest that some victims did not receive appropriate medical care, nor was the regional poison center contacted regarding care. The full extent of health problems related to HF could be better quantified if usual surveillance sources, such as vital records, included unique coding for this acid.

Adult↗
PubMed1998

A toxic fusion protein accumulating between the mitochondrial membranes inhibits protein assembly in vivo.

When overexpressed in Saccharomyces cerevisiae, beta-galactosidase fusion proteins directed to the mitochondria are toxic, preventing growth of yeast cells on non-fermentable carbon sources (Emr, S. D., Vassarotti, A., Garrett, J., Geller, B. L., Takeda, M., and Douglas, M. G. (1986) J. Cell Biol. 102, 523-533). We show that such fusion proteins interfere with the assembly of respiratory complexes in the mitochondrial inner membrane, without blocking protein translocation. The gene YME1, encoding an ATP-dependent metalloprotease of the mitochondrial inner membrane, acts as a suppressor of this defect; a 3-fold overexpression of Yme1p is sufficient to restore respiratory complex assembly and mitochondrial function. Detailed knowledge of the topology and effect of the toxic beta-galactosidase fusion proteins will permit the identification and characterization of components that control protein sorting and protein assembly within the mitochondrial inner membrane.

ATP-Dependent Proteases↗
PubMedDate not supplied

Selecting high-priority hazardous chemicals for tri-national control: a maximum-utility method applied to Mexico.

The dispersion of persistent, bioaccumulative toxic chemicals poses risks to human health and the integrity of the ecosystem on a continental scale. Mexico, the United States, and Canada sought to add two pollutants to an existing list of four subject to North American Regional Action Plans (chlordane, DDT, mercury, PCBs). Mexican negotiators used results from an internal selection process, applying 14 criteria in five categories-physicochemical, health-endpoint, data quality/quantity, exposure potential, and control feasibility-to a baseline group of over 4,700 substances. Using policy analysis by the multiattribute maximum-utility method, progressive application of criteria and weighting algorithms acted like successive filters to identify priority lists of 15 and 7 substances/substance groups for Mexico. The 15 are: 1) benzo-a-pyrene (1 other PAHs); 2) cadmium; 3) heptachlor; 4) hexachlorobenzene; 5) lead; 6) lindane (+ other HCH isomers); 7) 2,3, 7,8-tetrachlorodibenzo-p-dioxin (&plus other PCDDs); 8) aldrin; 9) arsenic; 10) chromium; 11) carbon tetrachloride; 12) 3-3'-dichlorobenzidine; 13) dieldrin; 14) nickel; and 15) toxaphene. The first seven are the priority list of seven.

Algorithms↗
PubMedDate not supplied

Moving further upstream: from toxics reduction to the precautionary principle.

Early policies to reduce the amount of toxic waste in the environment focused on cleaning up downstream sources of pollution, such as toxic disposal sites. Public attention in the 1980s encouraged both industry and government to develop an alternative to this command-and-control approach. This article describes the emergence of that alternative-pollution prevention-and its application in Massachusetts through the 1989 Toxics Use Reduction Act. Pollution prevention focuses on the sources of pollution, both metaphorically and physically, more upstream than its predecessors. The success of the Toxics Use Reduction Act in Massachusetts helped create an opportunity where an alternative pollution prevention paradigm could develop. That paradigm, the precautionary principle, is popular among environment activists because it focuses further upstream than pollution prevention by calling attention to the role the social construction of risk plays in decisions regarding the use of hazardous substances. The authors examine the evolution of the precautionary principle through an investigation of three major pathways in its development and expansion. The article concludes with a discussion of the increased potential for protecting public health and the environment afforded by this new perspective.

Community Participation↗
PubMed1991

NTP technical report on the toxicity studies of Hexachloro-1,3-butadiene in B6C3F1 Mice (Feed Studies) (CAS No. 87-68-3).

Two-week and 13-week toxicity studies of hexachloro-1,3-butadiene incorporated in the diet were conducted in B6C3F1 mice. Groups of five mice of each sex received diets containing 0, 30, 100, 300, 1,000, or 3,000 ppm hexachloro-1,3-butadiene for 15 days. Toxic responses in the 2-week studies, primarily in the higher dose groups, included abnormal clinical signs (lethargy, hunched posture, rough hair coats, light sensitivity, and/or in coordination), deaths (all mice in the two highest dose groups died by day 7), body and organ weight depression, and gross and histopathologic changes. The most prevalent microscopic lesion, seen in all hexachloro-1,3-butadiene-dosed mice, was renal tubular cell necrosis and/or regeneration. Regeneration was seen in lower dose groups. In addition to kidney lesions, histopathologic changes were also seen in the liver (hepatocyte necrosis, cytoplasmic vacuolization), lymphoid tissues (lymph node necrosis, depletion), and testis (seminiferous tubule giant cells) of mice in the two highest dose groups which died during the first week of the studies. Thirteen-week studies were conducted in which groups of 10 mice per sex received 0,1, 3,10, 30, or 100 ppm hexachloro-1,3-butadiene in feed (corresponding to doses of 0, 0.1, 0.4, 1.5, 4.9, or 16.8 mg/kg per day for males and 0.2, 0.5, 1.8, 4.5, or 19.2 mg/kg per day for females). No compound-related clinical signs or deaths were observed. Compared with controls, body weight gain was reduced in males receiving 30 and 100 ppm (-49% and -56%, respectively) and females receiving 100 ppm (-47%). Kidney weights were reduced in the males receiving 30 and 100 ppm and females receiving 100 ppm. A compound-related increase in tubular cell regeneration in the renal cortex occurred in male and female mice. This lesion, characterized by a diffuse increase in basophilia of the tubular epithelial cytoplasm and an increase in the number of nuclei, increased in severity with increased dose. The motility of sperm from dosed mice was lower, though not dose related, than that from controls. Female mice were more susceptible to the toxicity of hexachloro-1,3-butadiene than male mice. Based on the histopathologic evaluations, the no-observed-adverse-effect level appeared to be 10 ppm for the male mice in this 13-week study; no such level was identified for the female mice. Synonyms: HCBD; hexachlorobutadiene; 1,1,2,3,4,4-hexachloro-1,3- butadiene; perchlorobutadiene; C 46; Dolen-Pur, (NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.)

Journal Article↗
PubMed2002

Endotoxin activity of Moraxella osloensis against the grey garden slug, Deroceras reticulatum.

Moraxella osloensis is a gram-negative bacterium associated with Phasmarhabditis hermaphrodita, a slug-parasitic nematode that has prospects for biological control of mollusk pests, especially the grey garden slug, Deroceras reticulatum. This bacterium-feeding nematode acts as a vector that transports M. osloensis into the shell cavity of the slug, and the bacterium is the killing agent in the nematode-bacterium complex. We discovered that M. osloensis produces an endotoxin(s), which is tolerant to heat and protease treatments and kills the slug after injection into the shell cavity. Washed or broken cells treated with penicillin and streptomycin from 3-day M. osloensis cultures were more pathogenic than similar cells from 2-day M. osloensis cultures. However, heat and protease treatments and 2 days of storage at 22 degrees C increased the endotoxin activity of the young broken cells but not the endotoxin activity of the young washed cells treated with the antibiotics. This suggests that there may be a proteinaceous substance(s) that is structurally associated with the endotoxin(s) and masks its toxicity in the young bacterial cells. Moreover, 2 days of storage of the young washed bacterial cells at 22 degrees C enhanced their endotoxin activity if they were not treated with the antibiotics. Furthermore, purified lipopolysaccharide (LPS) from the 3-day M. osloensis cultures was toxic to slugs, with an estimated 50% lethal dose of 48 microg per slug, thus demonstrating that the LPS of M. osloensis is an endotoxin that is active against D. reticulatum. This appears to be the first report of a biological toxin that is active against mollusks.

Animals↗
PubMed1995

Cocaine and benzoylecgonine constrict cerebral arteries by different mechanisms.

This study was designed to determine possible mechanisms underlying the vasoconstrictor activity of cocaine and its principal metabolite, benzoylecgonine (BE) in cat isolated cerebral arteries. The arteries constricted significantly in response to single doses of cocaine, BE and norepinephrine (NE; (P < 0.05). After 6-OHDA treatment to remove adrenergic nerve endings, NE-induced constrictions were essentially unchanged from those before treatment. Denervated arteries exposed to cocaine dilated significantly (P < 0.05) but those exposed to BE constricted as much as before denervation. Following exposure to prazosin and yohimbine, arterial constrictions to NE and cocaine were significantly reduced from control (P < 0.05) but the BE-induced constriction was unchanged. Ryanodine eliminated the cocaine-induced contraction (P < 0.05) whereas verapamil eliminated the BE response (P < 0.05). These data suggest that while cocaine's vasoconstrictor action may be significantly mediated through adrenergic transmission, BE may act through a mechanism involving calcium (Ca2+) channels. Cocaine levels peak and decline in the body more rapidly than BE levels which can remain detectable for days. This study suggests there may also be different pharmacological mechanisms as well as temporal differences underlying the vasoreactivity of these two substances. Our findings may have implications for pharmacological management of cocaine-induced toxic vascular events.

Animals↗