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This investigation describes histological and cytometrical changes of cortical and medullary tissue of adrenal in rats under the acute stress of O-chlorobenzylidene malononitrile (10 mg/kg and 20 mg/kg). It has been observed that after injection of CS, the adrenal gland showed histological changes both in the cortical and medullary region.
This communication describes histological changes in the thyroid gland of rats under the acute stress of O-chlorobenzylidene malononitrile (CS) 10 mg/kg and 20 mg/kg). It has been observed that CS, when injected, causes histological changes in the thyroid of varying degrees, depending on the dose used.
The biomarker 2-(1-{6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([(18)F]FDDNP) is used as a positron emission tomography (PET) imaging probe for Alzheimer's disease and other neurodegenerative diseases. A high-yield and fully automated synthesis of [(18)F]FDDNP--along with the synthesis and characterization of non-radioactive FDDNP, a fluorescent probe derived from 2-(1,1-dicyanopropenyl-2)-6-dimethylaminonaphthalene (DDNP)--are reported. Radiofluorination of the tosyloxy precursor 2-{[6-(2,2-dicyano-1-methylvinyl)-2-naphthyl](methyl)amino}ethyl-4-methylbenzenesulfonate (DDNPTs) with K(18)F/Kryptofix 2.2.2. yielded chemically (>99%) and radiochemically (>99%) pure [(18)F]FDDNP in high radiochemical yields (40-60%; n> 120), with specific activities ranging from 4 to 8 Ci/mumol at the end of synthesis (90 minutes). Both remote, semiautomated and automated synthesis procedures are described. Either approach provides a reliable method for production of large quantities (110-170 mCi from 500 mCi of [(18)F]fluoride) of [(18)F]FDDNP allowing for multiple PET experiments in the same day or for distribution of the tracer from a single cyclotron facility to PET imaging centers at various geographical distances.
A sensitive method for determination of sialic acids by monitoring the fluorescence produced with malononitrile in borate buffer has been established. Measurement of the fluorescence intensity of the reaction mixture at 430 nm with irradiation at 360 nm allowed determination of 3-60 nmol of sialic acids with high reproducibility. A few amino sugars and deoxy sugars, as well as catecholamines reacted with this reagent; however other carbohydrates, amino acids, amines, aldehydes, and carboxylic acids including alpha-keto acids, etc., showed little reactivity. This method was successfully applied to postcolumn fluorescence labeling of sialic acids in high-performance liquid chromatography.
The use of tear gas in controlling riots has been an accepted practice in many countries for the past four decades. In a recent event, a large quantity of tear-gas canisters were used during a situation of unrest in a Hong Kong Refugees' Detention Centre. We report 96 cases of acute burn injury as an unpredicted side effect of o-chlorobenzylidene malononitrile (CS) tear gas. There were 47 females and 49 males with an age ranging between < 1 to 51 years. These burns were categorized as minor burns, with the total body surface area (TBSA) ranging from 1 to 8 per cent with mean percentage of 3. Most of the patients sustained superficial or partial-skin thickness injuries. Only two patients were admitted to the Prince of Wales Hospital Burns Centre because of deeper burns; debridement and skin grafting was required in one of them. The mechanism of burn injury was due to the flame generated from the grenade explosion, direct contact between the hot canister and the victim's skin, and the effect of the chemical powder inside the canisters when it splashed onto the victim's body. We suggest that the noxious transient effects of tear gas are underestimated, furthermore varying cutaneous effects and deep burns may result from its uncontrolled use during riots. There is a continuing need to reassess the potential toxic effects of CS tear gas as a riot control agent and to debate whether its future use can be condoned under any circumstances.
The effect of O-chlorobenzylidene malononitrile (CS) on the immune system was studied in mice given 8 and 16 mg/kg body weight i.p. of the compound, daily for 10 days. The humoral immune response to SRBC was suppressed at both doses, as determined by the antibody producing cells in the spleen. To find out whether the immunosuppression observed was due to the indirect effect of CS on the nutritional status and endocrine balance, serum proteins and corticosterone levels were measured. While the serum proteins did not alter, corticosterone levels rose significantly only in mice receiving higher dose of CS.
In a hazardous materials event in 2002, the unannounced presentation of 3 symptomatic, contaminated patients to an emergency department (ED) resulted in secondary contamination of 2 ED personnel who experienced skin, eye, and respiratory irritation. The material that caused these injuries was o-chlorobenzylidene malononitrile, a white powder with a peppery odor used largely as a tear gas and riot-control agent. Secondary contamination can cause adverse symptoms and injuries in ED personnel, further contaminate the ED, and potentially lead to costly ED closures and evacuations. To prevent secondary exposure, EDs can educate their staff about the potential for secondary contamination, implement a team approach for handling contaminated patients, establish decontamination protocols, ensure proper selection of and training in the use of personal protective equipment, and simulate drills for receiving contaminated patients.
Tear gases are largely used to control civil unrest. Their incapacitating effects involve the eyes, skin, and respiratory tract. We aimed to evaluate the effects of ortho-chlorobenzylidene malononitrile (CS) and oleoresin capsicum (OC) on ciliary beat frequency (CBF) of mouse tracheal rings. Addition of 0.05% OC or 0.01% CS induced a progressive decrease in CBF, from 11.5+/-0.5 to 4+/-0.1 Hz (P<0.05) and from 12.5+/-0.5 to 2.5+/-0.1 Hz (P<0.05), respectively, 30 min after exposure to the tear gas. Addition of exogenous ATP inhibited the effect of OC, suggesting that ATP could be used to counteract these adverse effects on CBF. However, ATP was inefficient against CS. Methylene blue and H7 inhibited the effects of OC, whereas indomethacin had no effect. None of these drugs affected the inhibitory action of CS. These results suggest that the inhibitory effect of OC is mediated through the guanylate cyclase-dependent pathway or protein kinase C-dependent phosphorylation. Another mechanism is probably involved in CS-induced inhibitory effect. Histological analysis of the trachea revealed an increase in mucus secretion after exposure to OC, and cytoplasmic vacuoles in epithelial cells after exposure to CS.
Epidemiological studies have suggested that the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the relative risk of Alzheimer's disease (AD). The possible neuroprotection by NSAIDs in AD is generally attributed to anti-inflammatory activity. An additional mode of drug action may involve anti-aggregation of beta-amyloid (Abeta) peptides by commonly used NSAIDs. We utilized in vitro competition assays, autoradiography, and fluorescence microscopy with AD brain specimens to demonstrate concentration-dependent decreases in the binding of the in vivo molecular imaging probe, 2-(1-[6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrile ([(18)F]FDDNP), against (S)-naproxen and (R)- and (S)-ibuprofen (but not diclofenac) to Abeta fibrils and ex vivo Abeta senile plaques. Conversely, in vitro amyloid dyes Congo Red and Thioflavine T were demonstrated in the same experiments not to bind to the FDDNP binding site. FDDNP and the NSAIDs that share the same binding site also exhibit anti-aggregation effects on Abeta peptides, suggesting that the shared binding site on Abeta fibrils and plaques may be a site of anti-aggregation drug action. Our results indicate for the first time the binding of select NSAIDs to plaques, specifically to the binding site of the molecular imaging probe [(18)F]FDDNP. Our understanding of the molecular requirements of FDDNP binding may help in the optimization of the Abeta anti-aggregation potency of experimental drugs. [(18)F]FDDNP has been used to image plaques in vivo with positron emission tomography (PET), and investigations into the influence of Abeta anti-aggregation on the risk-reduction effects of NSAIDs on AD could utilize [(18)F]FDDNP and PET in determining the occupancy rate of NSAIDs and experimental drugs in plaques in the living brain of AD patients.
The FTIR spectra (4000-100 cm(-1)) and Raman spectra (3500-30 cm(-1)) of 2-[5,5-dimethyl-3-(2-phenyl-vinil)-cyclohex-2-enylidene]-malononitrile in solid state were measured. In addition, the structure and harmonic vibrational frequencies of this molecule were theoretically evaluated using B3LYP density functional methods. The computed vibrational frequencies are used to determine the types of molecular motions associated with each of the experimental bands observed. Bond length alternation (BLA) was established. Comparison with the experimental spectra provides important information about the ability of this computational method to describe the vibrational modes in this type of "push-pull" systems with potential non-linear optical applications.
2-[(2E)-3-(4-tert-Butylphenyl)-2-methylprop-2-enylidene]malononitrile (DCTB) is a nonpolar, aprotic matrix and was used in the analysis of a variety of compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The classes of compounds include coordination compounds, organometallics, conjugated organic compounds (including porphyrins and phthalocyanines), carbohydrates, calixarenes, and macrocycles. For some samples, comparisons are made with spectra acquired with the use of 1,8,9-trihydroxyanthracene (dithranol), 2,5-dihydroxybenzoic acid, and 2,4,6-trihydroxyacetophenone matrixes. Traditionally, the majority of these compounds would have been analyzed by fast-atom bombardment (FAB), liquid secondary ion mass spectrometry (LSIMS), or electrospray techniques, but this work shows that MALDI-TOFMS using DCTB has advantages over these techniques, particularly FAB and LSIMS. Certain limitations of DCTB are noted, for example, in the analysis of water-soluble compounds such as peptides, proteins, and oligonucleotides, and good working practices for the use of the matrix are also outlined.
[reaction: see text] An efficient method for the synthesis of 1,7-enyne derivatives via a palladium-catalyzed three-component assembly of arylethylidene malononitriles, allylic chlorides, and allenylstannanes is described.
Under mechanical milling conditions, direct reductive benzylizations of malononitrile and 4-methylaniline by aromatic aldehydes were achieved using a Hantzsch 1,4-dihydropyridine as the reductant.
1. The effects of o-chlorobenzylidene malononitrile (CS) have been studied on several isolated organs and tissues, anaesthetized animals and cat encéphale isolé preparations.2. On the isolated guinea-pig ileum an initial dose of CS produced a small, non-maintained contraction. Subsequent doses had reduced effects. There was no effect on peristalsis when the substance was given intraluminally.3. No significant effects of CS were detected on the rat phrenic nerve-diaphragm preparation, the isolated perfused rabbit heart or on the contractor response of the indirectly stimulated cat tibialis muscle.4. In the cat encéphale isolé preparation 1 mg/kg (i.v.) produced a brief period of electrocortical alerting but no abnormal activity in the electrocorticogram. Doses in excess of 10 mg/kg produced cortical depression.5. Intravascular injection into the chloralose anaesthetized cat resulted typically in a pressor response accompanied by a brief period of apnoea. The threshold dose for the pressor response varied with the route of administration, but generally lay between 2.5 and 12.5 mug/kg; the threshold dose for apnoea was slightly higher. Small variations in this pattern of response were seen with different species and other anaesthetics.6. When administered by stomach tube to chloralose anaesthetized cats, CS produced no measurable effects at doses of up to 100 mg/kg.7. No changes in blood pressure or respiration were detected in anaesthetized cats given pure CS aerosol for 1 h in concentrations of between 345 mg/m(3) and 1.39 g/m(3) via a tracheal cannula or through the upper respiratory tract. Pure CS solution given by slow intravenous infusion at a similar dose and over a similar period produced significant effects on blood pressure and respiration.8. Pyrotechnically generated (grenade) CS produced variable effects when given by inhalation in concentrations of between 460 and 1,040 mg/m(3) for 1 hour. Respiratory depression, possibly reflex in nature, regularly occurred when the material was given via the upper respiratory tract, and respiratory stimulation occurred when it was given via a tracheal cannula.9. Some cats were pre-exposed to a dose of 500 (mg/min)/m(3) on 4 successive days and on the fifth day anaesthetized and exposed to high concentrations of grenade CS. Three out of six cats died during or after this final exposure compared to one out of six among animals not so pre-exposed. The general pattern of response to the final exposure to CS in the two groups was similar.
Ventilation minute volume, tidal volume and cardiac frequency during submaximal exercise have been measured in healthy young soldier volunteers exposed to O-chlorobenzylidene malononitrile (CS) and ammonia gas in concentrations respectively of 0.16 to 4.4 mg.m(-3) and 50 to 344 mg.m(-3). The response of ventilation minute volume to the two gases is apparently similar; both gases cause a reduction of, on average 6%. With low doses this reflects a diminution in respiratory frequency whereas with higher doses it is due to a reduction in tidal volume which is accompanied by tachypnoea. The findings may result from stimulation successively of receptors in the larynx and of irritant receptors in the large airways of the lung. The pain which is a feature of exposure to CS but not to ammonia is due to stimulation of other so far unidentified receptors. Neither gas has a direct effect upon the exercise cardiac frequency.
Malononitrile dimer was administered to mice by single or by chronic (40 day) injections. The concentration of RNA in neurons of the brain was determined on histological sections by means of azure B staining. The nucleolus and Nissl substance of the several types of large neurons studied had a significantly higher concentration of RNA in the drug-injected than in the control animals.
Tear gases are largely used to control civil unrest. Their incapaciting effects involve eyes, skin and respiratory tract. This study was performed to compare acute respiratory effects of o-chlorobenzylidene malononitrile (CS), oleoresin capsicum (OC) and their respective solvents in awake rats, using an integrated system of nose-only exposure and multiple monitoring of breathing. Aerosols were generated by a Collison Nebulizer from the solutions held in tear gas sprays. The reduction of minute ventilation, observed during a 5 min exposure, was significantly more important with CS than with OC: minute ventilation represented 29+/-8 and 50+/-6% of pre-exposure minute ventilation respectively (P<0.05). The reduction of minute ventilation observed with CS and OC solvents alone was not significantly different from that observed with the tear gases themselves. The decrease in minute ventilation observed, between the second and the fifth minute of exposure, was of the same level for repeated exposure separated by 24 h. Time necessary to recover to 80% of pre-exposure minute ventilation was not significantly different between the two tear gases: 722+/-272 and 691+/-262 s for CS and OC respectively (NS). Histological analysis of the trachea, performed at the end of exposures, revealed an increase in mucus secretion after exposure to OC and cytoplasmic vacuoles in epithelial cells after exposure to CS. In the lungs, interstitial oedema was observed after exposure to OC and emphysema after exposure to CS.
Irritant incapacitants, also called riot control agents, lacrimators and tear gases, are aerosol-dispersed chemicals that produce eye, nose, mouth, skin and respiratory tract irritation. Tear gas is the common name for substances that, in low concentrations, cause pain in the eyes, flow of tears and difficulty in keeping the eyes open. Only three agents are likely to be deployed: (i) 1-chloroacetophenone (CN); (ii) 2-chlorobenzylidene malononitrile (CS); or (iii) dibenz[b,f]-1,4-oxazepine (CR). CN is the most toxic lacrimator and at high concentrations has caused corneal epithelial damage and chemosis. It has accounted for at least five deaths, which have resulted from pulmonary injury and/or asphyxia. CS is a 10-times more potent lacrimator than CN but is less systemically toxic. CR is the most potent lacrimator with the least systemic toxicity and is highly stable. CN, CS and CR cause almost instant pain in the eyes, excessive flow of tears and closure of the eyelids, and incapacitation of exposed individuals. Apart from the effects on the eyes, these agents also cause irritation in the nose and mouth, throat and airways and sometimes to the skin, particularly in moist and warm areas. In situations of massive exposure, tear gas, which is swallowed, may cause vomiting. Serious systemic toxicity is rare and occurs most frequently with CN; it is most likely to occur when these agents are used in very high concentrations within confined non-ventilated spaces. Based on the available toxicological and medical evidence, CS and CR have a large safety margin for life-threatening or irreversible toxic effects. There is no evidence that a healthy individual will experience long-term health effects from open-air exposures to CS or CR, although contamination with CR is less easy to remove.